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Publication numberCN103421057 A
Publication typeApplication
Application numberCN 201310353598
Publication dateDec 4, 2013
Filing dateAug 14, 2013
Priority dateAug 14, 2013
Also published asCN103421057B
Publication number201310353598.8, CN 103421057 A, CN 103421057A, CN 201310353598, CN-A-103421057, CN103421057 A, CN103421057A, CN201310353598, CN201310353598.8
Inventors徐云根, 屠哲玮, 何广卫, 唐琰, 何书英, 孙菁, 司崇静, 刘坤
Applicant合肥医工医药有限公司, 中国药科大学
Export CitationBiBTeX, EndNote, RefMan
External Links: SIPO, Espacenet
Combretastatin amino sugar conjugate and preparation method and medical appliance thereof
CN 103421057 A
Abstract
The invention relates to the field of medical chemistry, in particular to a Combretastatin (A-4, CA-4) amino sugar conjugate, and a preparation method and tumor blood vessel inhibition thereof. The Combretastatin amino sugar conjugate is good in water solubility. Pharmacology experiments show that the compound is high in inhibition of human umbilical vascular endothelial cell proliferation and good in inhibition of mice tumor cells. Therefore, the compound of formula I and the crystal-water-containing compound thereof can be used for treating various diseases related to angiogenesis, and the diseases include various cancers and chronic inflammation and other blood vessel originated diseases.
Claims(7)  translated from Chinese
1.通式(I)的化合物或其水合物: 1. Formula (I) compound or a hydrate thereof:
Figure CN103421057AC00021
其中R代表:H、卤素、羟基X1〜C6的烷氧基、C1〜C6的烷基、羟甲基、硝基、氨基、甲酰胺基、乙酰氨基或氨甲基; G-NH-代表: Wherein R represents: H, halogen, hydroxy X1~C6 alkoxy, C1~C6 alkyl, hydroxymethyl, nitro, amino, formamido, acetamido or aminomethyl; G-NH- Representative:
Figure CN103421057AC00022
2.权利要求1的化合物或其水合物,其中R代表:H、齒素、羟基、甲基、羟甲基、硝基或M基; G-NH-代表: Compound or a hydrate thereof according to claim 1, wherein R represents: H, teeth, hydroxy, methyl, hydroxymethyl, a nitro group, or M; G-NH- Representative:
Figure CN103421057AC00023
3.权利要求2的化合物或其水合物,其中R代表:H、羟基或氨基; G-NH-代表: Compound or a hydrate thereof according to claim 2, wherein R represents: H, a hydroxyl group or an amino group; G-NH- Representative:
Figure CN103421057AC00031
4.权利要求1至3中任一项的化合物或其水合物,其中的水合物以结晶水的形式存在,结晶水的摩尔当量从0.5到10。 1-3 or a hydrate thereof A compound according to any preceding claim, wherein the crystalline form of the hydrate water in the presence of water of crystallization from 0.5 to 10 molar equivalents.
5.一种药物组合物,其中含有权利要求1至4中任一项的化合物或其水合物和药学上可接受的载体。 5. A pharmaceutical composition comprising a compound or a hydrate thereof according to claim and a pharmaceutically acceptable carrier according to any one of 1-4.
6.权利要求1至4中任一项的化合物或其水合物在制备治疗血管生成性疾病的药物中的用途。 1-4 A compound or a hydrate thereof for the preparation of any therapeutic angiogenic diseases in claim.
7.权利要求6的用途,其中血管生成性疾病是肿瘤或慢性炎症。 Use according to claim 6, wherein the angiogenic disease is cancer or chronic inflammation.
Description  translated from Chinese

康普瑞汀氨基糖缀合物、其制法及其医药用途 CommScope Reading amino sugar conjugates, their preparation and pharmaceutical use

技术领域 Technical Field

[0001] 本发明涉及药物化学领域,具体涉及一类康普瑞汀(Combretastatin A_4, CA-4)与氨基糖的缀合物、它们的制备方法、以及对肿瘤血管的抑制作用。 [0001] The present invention relates to the field of pharmaceutical chemistry, in particular to a class of CommScope Reading (Combretastatin A_4, CA-4) with an amino sugar conjugates, methods for their preparation, as well as the inhibition of tumor blood vessels.

背景技术 Background

[0002] 肿瘤血管阻断剂(Vascular Disrupting Agents, VDA)能够选择性破坏已形成的肿瘤血管网的内皮细胞和周细胞,进而快速切断肿瘤血供,诱发肿瘤细胞发生缺血坏死,能有效阻止肿瘤的生长和转移。 [0002] inhibitor of tumor blood vessels (Vascular Disrupting Agents, VDA) has been formed to selectively destroy tumor vascular endothelial cells and pericytes network, and then quickly cut off the blood supply to tumors, tumor cells induce necrosis, can effectively prevent tumor growth and metastasis. 因此,VDA与传统抗肿瘤药物相比有巨大的优势,但目前在临床研究的VDA存在心血管及神经系统毒性。 Therefore, VDA, compared with the conventional anticancer drugs has a huge advantage, but the presence of cardiovascular and nervous system toxicity in clinical studies VDA. 因此开发疗效好、毒副作用小的VDA是目前该类药物的研究重点。 Therefore the development of good efficacy, side effects VDA is the research focus of these drugs.

[0003] 康普瑞汀是从南非的Combretum Caffnom树皮中分离出来的小分子VDA,其能结合血管内皮细胞微管蛋白β亚基的秋水仙碱结合位点,导致微管蛋白的聚合,进而改变其内皮细胞的骨架结构与形态,增强其血管渗透性、扰乱血流,从而引起肿瘤血管内皮细胞凋亡,导致次级肿瘤细胞死亡。 [0003] CommScope Reading is separated from South Africa Combretum Caffnom bark of small molecule VDA, which can bind to the colchicine binding site of vascular endothelial β subunit of tubulin, leading to the polymerization of tubulin, thus changing its skeletal structure and morphology of endothelial cells, enhance its vascular permeability, disrupt blood flow, causing the tumor vascular endothelial cell apoptosis, leading to secondary tumor cell death. 尽管康普瑞汀具有潜在的生物活性,但其低水溶性和低生物利用度限制了进一步的应用。 Although CommScope Reading potentially biologically active, but its low water solubility and low bioavailability limit further application. 因此,人们对CA-4的结构进行改造,以期获得具有更好水溶性、化学稳定性和生物利用度的活性先导物。 Therefore, it is the structure of CA-4 to be transformed in order to obtain a better solubility, chemical stability and activity of the lead compound bioavailability. 研究发现,在康普瑞汀的双键上引入一个胺甲酰基后得到的化合物(如CA-4-1〜CA-4-4)的细胞毒作用弱于康普瑞汀,但对微管蛋白聚合 The compound (such as CA-4-1~CA-4-4) study found that the introduction of a carbamoyl Reading on CommScope double bond obtained by weaker cytotoxicity CommScope Reading, but microtubules protein aggregation

的抑制活性强于康普瑞汀。 The inhibitory activity is stronger than CommScope Reading.

[0004] [0004]

Figure CN103421057AD00041

[0005] 氨基糖类化合物具有良好的分子识别性和生物相容性等优点,某些N-酰基氨基糖衍生物具有一定的肿瘤血管生成抑制活性。 [0005] amino saccharide compounds have good molecular recognition and biocompatibility, etc., some of N- acylamino sugar derivatives have certain tumor angiogenesis-inhibiting activity. 专利CN101591364和CN101591369公开了一系列N-糖基苯丙烯酰胺衍生物,如化合物XY018和XY023对bFGF (basic fibroblastgrowth factor,碱性成纤维细胞生长因子)刺激的人脐静脉内皮细胞的增殖具有良好的抑 Patents CN101591364 CN101591369 discloses a series of N- and sugar phenylpropenamides derivatives such as compound XY018 and XY023 of bFGF (basic fibroblastgrowth factor, basic fibroblast growth factor) stimulated proliferation of human umbilical vein endothelial cells with good curb

制作用。 Making use.

[0006] [0006]

Figure CN103421057AD00042

发明内容 DISCLOSURE

[0007] 本发明公开了一类通式I的化合物及其水合物。 [0007] The present invention discloses a class of compounds of Formula I and hydrates thereof. 本发明的化合物具有良好的水溶性。 The compounds of this invention have good solubility in water. 药理实验显示,本发明的化合物对人脐静脉内皮细胞增殖具有较强的抑制作用,同时,部分化合物对人及小鼠肿瘤细胞也有较好的抑制作用。 Pharmacological experiments show that the compounds of the present invention in human umbilical vein endothelial cells has a strong inhibitory effect, at the same time, some of the compounds in human and mouse tumor cells and has a good inhibition. 因此,本发明的式I化合物及其含结晶水的化合物可以用于治疗各种与血管生成相关的疾病,这些疾病包括各种癌症和慢性炎症,以及其它血管原性的疾病。 Accordingly, the compounds of formula I of the present invention is a compound containing water of crystallization and can be used to treat various diseases associated with angiogenesis, such diseases include various cancers and chronic inflammation, and other angiogenic diseases.

[0008] 本发明的化合物通式I如下: [0008] The compounds of formula I of the invention as follows:

[0009] [0009]

Figure CN103421057AD00051

[0010] 其中R代表:H、卤素、羟基、Ci〜C6的烷氧基、C1〜C6的烷基、羟甲基、硝基、氨基、甲酰胺基、乙酰氨基或氨甲基。 [0010] wherein R represents: H, halogen, hydroxy, Ci~C6 alkoxy, C1~C6 alkyl, hydroxymethyl, nitro, amino, formamido, acetamido, or aminomethyl.

[0011] R优选代表:H、卤素、羟基、甲基、羟甲基、 硝基或氨基。 [0011] R preferably represents: H, halogen, hydroxy, methyl, hydroxymethyl, nitro or amino.

[0012] R进一步优选代表:H、羟基或氨基。 [0012] R more preferably represents: H, hydroxy or amino.

[0013] 其中G - NH-代表以下任一结构: [0013] where G - NH- on behalf of any of the following structure:

[0014] [0014]

Figure CN103421057AD00052
Figure CN103421057AD00061

[0018] 本友明化合物的水合物也具有与化合物同样的疗效,其中的水合物以结晶水的形式存在,结晶水的摩尔当量从0.5到10。 [0018] The compounds of the Friends hydrate has the same effect with the compound, wherein the hydrate crystalline form of the presence of water, water of crystallization from 0.5 to 10 molar equivalents.

[0019] 本发明部分化合物是: [0019] Some compounds of the present invention are:

[0020] N- (2,3,4,6-四_0_ 乙酰基-1-脱氧_ β -D-吡喃葡萄糖基)_ (E) _3_ (3' -羟基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-1) [0020] N- (2,3,4,6- four _0_-acetyl-1-deoxy-_ β -D- glucopyranosyl) _ (E) _3_ (3 '- hydroxy-4'-methoxy phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-1)

[0021] N-(2, 3,4, 6-四_0_ 乙酰基-1-脱氧_ β _D_ 吡喃半乳糖基)-(E) _3_ (3' -羟基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-2) [0021] N- (2, 3,4, 6- acetyl-1-deoxy-four _0_ _ β _D_-galactopyranosyl) - (E) _3_ (3 '- hydroxy-4'-methoxyphenoxy yl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-2)

[0022] N-(I, 3,4,6-四_0_ 乙酰基_2_ 脱氧-β -D-吡喃葡萄糖基)_ (E) _3_ (3' -羟基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-3) [0022] N- (I, 3,4,6- four _0_ acetyl _2_ deoxy -β -D- glucopyranosyl) _ (E) _3_ (3 '- hydroxy-4'-methoxyphenoxy yl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-3)

[0023] N-(I, 3,4,6-四_0_ 乙酰基_2_ 脱氧-β -D-吡喃半乳糖基)_ (E) _3_ (3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-4) [0023] N- (I, 3,4,6- four _0_ acetyl _2_ deoxy -β -D- galactopyranosyl) _ (E) _3_ (3 '- hydroxy - 4' - methoxy phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-4)

[0024] N-(2,3,4,6-四_0_乙酰基_1_脱氧-β-D-吡喃葡萄糖基)-(Ε)-3_(4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-5) [0024] N- (2,3,4,6- four _0_ acetyl _1_ deoxy -β-D- glucopyranosyl) - (Ε) -3_ (4'- methoxyphenyl) 2- (3 ', 4', 5 '_ trimethoxyphenyl) acrylamide (1-5)

[0025] N-(2,3,4,6-四_0_乙酰基_1_脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-6) [0025] N- (2,3,4,6- four _0_ acetyl _1_ deoxy -β-D- galactopyranosyl) - (Ε) -3_ (4'- methoxyphenyl ) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-6)

[0026] N-(l,3,4,6-四_0_乙酰基_2_脱氧-β-D-吡喃葡萄糖基)-(Ε)_3-(4'_甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-7) [0026] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- glucopyranosyl) - (Ε) _3- (4'_ methoxyphenyl) 2- (3 ', 4', 5 '_ trimethoxyphenyl) acrylamide (1-7)

[0027] N-(l,3,4,6-四_0_乙酰基_2_脱氧-β-D-吡喃半乳糖基)-(Ε)_3-(4'_甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-8) [0027] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- galactopyranosyl) - (Ε) _3- (4'_ methoxyphenyl ) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-8)

[0028] N-(2,3,4,6-四_0_乙酰基-1-脱氧-β-D-吡喃葡萄糖基)-(E) -3- (3' -氯-4' -甲氧基苯基)-2- (3”,4”,5” -三甲氧基苯基)丙烯酰胺(1_9) [0028] N- (2,3,4,6- four _0_-acetyl-1-deoxy -β-D- glucopyranosyl) - (E) -3- (3 '- chloro-4' - methoxyphenyl) -2- (3 ', 4', 5 '- trimethoxyphenyl) acrylamide (1_9)

[0029] N-(2,3,4,6-四_0_乙酰基-1-脱氧-β-D-吡喃半乳糖基)-(Ε)-3-(3'_氯-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_10) [0029] N- (2,3,4,6- four _0_-acetyl-1-deoxy -β-D- galactopyranosyl) - (Ε) -3- (3'_ chloro-4 ' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1_10)

[0030] N-(l,3,4,6-四_0_乙酰基_2_脱氧-β-D-吡喃葡萄糖基)-(Ε)-3-(3'_氯-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-1l) [0030] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- glucopyranosyl) - (Ε) -3- (3'_ chloro-4'- methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-1l)

[0031] N-(l,3,4,6-四_0_乙酰基_2_脱氧-β-D-吡喃半乳糖基)-(Ε)-3-(3'_氯-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_12) [0031] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- galactopyranosyl) - (Ε) -3- (3'_ chloro-4 ' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1_12)

[0032] N-(2,3,4,6-四_0_乙酰基-1-脱氧-β-D-吡喃葡萄糖基)-(Ε)-3-(3'_氟-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_13) [0032] N- (2,3,4,6- four _0_-acetyl-1-deoxy -β-D- glucopyranosyl) - (Ε) -3- (3'_-fluoro-4'- methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1_13)

[0033] N-(2,3,4,6-四_0_乙酰基-1-脱氧-β-D-吡喃半乳糖基)-(E)-3-(3'_氟-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_14) [0033] N- (2,3,4,6- four _0_-acetyl-1-deoxy -β-D- galactopyranosyl) - (E) -3- (3'_-fluoro-4 ' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1_14)

[0034] N-(l,3,4,6-四_0_乙酰基_2_脱氧-β-D-吡喃葡萄糖基)-(Ε)-3-(3'_氟-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_15) [0034] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- glucopyranosyl) - (Ε) -3- (3'_-fluoro-4'- methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1_15)

[0035] N-(l, 3, 4, 6-四_0_乙酰基_2_脱氧-β-D-吡喃半乳糖基)-(Ε)-3-(3'_氟-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_16) [0035] N- (l, 3, 4, 6- acetyl _2_ four _0_ deoxy -β-D- galactopyranosyl) - (Ε) -3- (3'_-fluoro-4 ' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1_16)

[0036] N-(2,3,4,6-四_0_ 乙酰基-1-脱氧_ β _D_ 吡喃葡萄糖基)-(E) _3_ (3',4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-17) [0036] N- (2,3,4,6- four _0_-acetyl-1-deoxy-_ β _D_ glucopyranosyl) - (E) _3_ (3 ', 4' - dimethoxyphenyl) 2- (3 ', 4', 5 '_ trimethoxyphenyl) acrylamide (1-17)

[0037] N-(2,3,4,6-四_0_ 乙酰基-1-脱氧_ β _D_ 吡喃半乳糖基)-(E) _3_ (3,,4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-18) [0037] N- (2,3,4,6- four _0_-acetyl-1-deoxy-_ β _D_-galactopyranosyl) - (E) _3_ (3,, 4 '- dimethoxyphenyl ) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-18)

[0038] N-(l,3,4,6-四_0_ 乙酰基_2_ 脱氧-β-D-吡喃葡萄糖基)-(E) _3_ (3,,4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-19) [0038] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- glucopyranosyl) - (E) _3_ (3,, 4 '- dimethoxyphenyl ) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-19)

[0039] N-(l,3,4,6-四_0_ 乙酰基_2_ 脱氧-β-D-吡喃半乳糖基)-(E) _3_ (3,,4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-20) [0039] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- galactopyranosyl) - (E) _3_ (3,, 4 '- dimethoxybenzene yl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-20)

[0040] N- (2,3,4,6-四_0_ 乙酰基-1-脱氧_ β -D-吡喃葡萄糖基)_ (E) _3_ (3' -硝基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-21) [0040] N- (2,3,4,6- four _0_-acetyl-1-deoxy-_ β -D- glucopyranosyl) _ (E) _3_ (3 '- nitro-4'-methoxy yl-phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-21)

[0041] N-(2, 3,4, 6-四_0_ 乙酰基-1-脱氧_ β _D_ 吡喃半乳糖基)-(E) _3_ (3' -硝基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-22) [0041] N- (2, 3,4, 6- acetyl-1-deoxy-four _0_ _ β _D_-galactopyranosyl) - (E) _3_ (3 '- nitro-4'-methoxy phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-22)

[0042] N-(I, 3,4,.6-四_0_ 乙酰基_2_ 脱氧-β -D-吡喃葡萄糖基)_ (E) _3_ (3' -硝基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-23) [0042] N- (I, 3,4, .6- four _0_ acetyl _2_ deoxy -β -D- glucopyranosyl) _ (E) _3_ (3 '- nitro-4'-methoxy yl-phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-23)

[0043] N-(I, 3,4,6-四_0_ 乙酰基_2_ 脱氧-β -D-吡喃半乳糖基)_ (E) _3_ (3' -硝基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-24) [0043] N- (I, 3,4,6- four _0_ acetyl _2_ deoxy -β -D- galactopyranosyl) _ (E) _3_ (3 '- nitro-4'-methoxy yl-phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-24)

[0044] N-(2, 3,4, 6-四_0_ 乙酰基-1-脱氧_ β _D_ 吡喃葡萄糖基)-(E) _3_ (3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-25) [0044] N- (2, 3,4, 6- acetyl-1-deoxy-four _0_ _ β _D_ glucopyranosyl) - (E) _3_ (3 '- amino-4'-methoxyphenyl ) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-25)

[0045] N- (2,3,4,6_ 四_0_ 乙酰基-1-脱氧_ β -D-吡喃半乳糖基)_ (E) _3_ (3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-26) [0045] N- (2,3,4,6_ four _0_-acetyl-1-deoxy-_ β -D- galactopyranosyl) _ (E) _3_ (3 '- amino-4'-methoxy phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-26)

[0046] N-(l,3,4,6-四_0_ 乙酰基_2_ 脱氧-β-D-吡喃葡萄糖基)-(E) _3_(3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-27) [0046] N- (l, 3,4,6- four _0_ acetyl _2_ deoxy -β-D- glucopyranosyl) - (E) _3_ (3 '- amino-4'-methoxyphenoxy yl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-27)

[0047] N-(I, 3,4,6-四_0_ 乙酰基_2_ 脱氧-β -D-吡喃半乳糖基)_ (E) _3_ (3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-28) [0047] N- (I, 3,4,6- four _0_ acetyl _2_ deoxy -β -D- galactopyranosyl) _ (E) _3_ (3 '- amino-4'-methoxy phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-28)

[0048] N-(1-脱氧_β -D-吡喃葡萄糖基)-(Ε)-3_(3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-29) [0048] N- (1- deoxy _β -D- glucopyranosyl) - (Ε) -3_ (3 '- hydroxy - 4' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-29)

[0049] N-(1-脱氧_β -D-吡喃半乳糖基)-(Ε)-3_(3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-30) [0049] N- (1- deoxy _β -D- galactopyranosyl) - (Ε) -3_ (3 '- hydroxy - 4' - methoxy-phenyl) -2- (3 ', 4' , 5 "_ trimethoxyphenyl) acrylamide (1-30)

[0050] N-(2-脱氧_β -D-吡喃葡萄糖基)-(Ε)-3_(3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-31) [0050] N- (2- deoxy _β -D- glucopyranosyl) - (Ε) -3_ (3 '- hydroxy - 4' - methoxy-phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-31)

[0051] N-(2-脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-32) [0051] N- (2- deoxy -β-D- galactopyranosyl) - (Ε) -3_ (3 '- hydroxy - 4' - methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-32)

[0052] N-(1-脱氧-β -D-吡喃葡萄糖基)-(E) -3- (4,-甲氧基苯基)-2- (3”,4”,5三甲氧基苯基)丙烯酰胺(1-33)[0053] N-(1-脱氧-β -D-吡喃半乳糖基)-(E) -3- (4,-甲氧基苯基)-2- (3”,4”,5,,-三甲氧基苯基)丙烯酰胺(1-34) [0052] N- (1- deoxy -β -D- glucopyranosyl) - (E) -3- (4, - methoxyphenyl) -2- (3 ', 4', 5-trimethoxy phenyl) acrylamide (1-33) [0053] N- (1- deoxy -β -D- galactopyranosyl) - (E) -3- (4, - methoxyphenyl) -2- (3 ', 4', 5 ,, - trimethoxyphenyl) acrylamide (1-34)

[0054] N- (2-脱氧-β -D-吡喃葡萄糖基)-(E) _3_ (4' -甲氧基苯基)_2_ (3”,4”,5三甲氧基苯基)丙烯酰胺(1-35) [0054] N- (2- deoxy -β -D- glucopyranosyl) - (E) _3_ (4 '- methoxyphenyl) _2_ (3', 4 ', 5-trimethoxyphenyl) propene amide (1-35)

[0055] N- (2-脱氧-β -D-吡喃半乳糖基)-(E) _3_ (4' -甲氧基苯基)_2_ (3”,4”,5三甲氧基苯基)丙烯酰胺(1-36) [0055] N- (2- deoxy -β -D- galactopyranosyl) - (E) _3_ (4 '- methoxyphenyl) _2_ (3', 4 ', 5-trimethoxyphenyl) acrylamide (1-36)

[0056] N-(1-脱氧-β-D-吡喃葡萄糖基)-(Ε)-3_(3' -氯_4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-37) [0056] N- (1- deoxy -β-D- glucopyranosyl) - (Ε) -3_ (3 '- chloro _4' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-37)

[0057] N-(1-脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(3' -氯_4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-38) [0057] N- (1- deoxy -β-D- galactopyranosyl) - (Ε) -3_ (3 '- chloro _4' - methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-38)

[0058] N-(2-脱氧-β-D-吡喃葡萄糖基)-(Ε)-3_(3' -氯_4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-39) [0058] N- (2- deoxy -β-D- glucopyranosyl) - (Ε) -3_ (3 '- chloro _4' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-39)

[0059] N-(2-脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(3' -氯_4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-40) [0059] N- (2- deoxy -β-D- galactopyranosyl) - (Ε) -3_ (3 '- chloro _4' - methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-40)

[0060] N-(1-脱氧-β-D-吡喃葡萄糖基)-(Ε)-3_(3' -氟-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-41) [0060] N- (1- deoxy -β-D- glucopyranosyl) - (Ε) -3_ (3 '- fluoro-4' - methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-41)

[0061] N-(1-脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(3' -氟-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-42) [0061] N- (1- deoxy -β-D- galactopyranosyl) - (Ε) -3_ (3 '- fluoro-4' - methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-42)

[0062] N-(2-脱氧-β-D-吡.喃葡萄糖基)-(Ε)-3_(3' -氟-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-43) [0062] N- (2- deoxy-pyran -β-D- glucosyl.) - (Ε) -3_ (3 '- fluoro-4' - methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-43)

[0063] N-(2-脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(3' -氟-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-44) [0063] N- (2- deoxy -β-D- galactopyranosyl) - (Ε) -3_ (3 '- fluoro-4' - methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-44)

[0064] N-(1-脱氧-β-D-吡喃葡萄糖基)-(Ε)-3_(3',4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-45) [0064] N- (1- deoxy -β-D- glucopyranosyl) - (Ε) -3_ (3 ', 4' - dimethoxyphenyl) -2- (3 ', 4', 5 "_ trimethoxyphenyl) acrylamide (1-45)

[0065] N-(1-脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(3',4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-46) [0065] N- (1- deoxy -β-D- galactopyranosyl) - (Ε) -3_ (3 ', 4' - dimethoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-46)

[0066] N-(2-脱氧-β-D-吡喃葡萄糖基)-(Ε)-3_(3',4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-47) [0066] N- (2- deoxy -β-D- glucopyranosyl) - (Ε) -3_ (3 ', 4' - dimethoxyphenyl) -2- (3 ', 4', 5 "_ trimethoxyphenyl) acrylamide (1-47)

[0067] N-(2-脱氧-β-D-吡喃半乳糖基)-(Ε)-3_(3',4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-48) [0067] N- (2- deoxy -β-D- galactopyranosyl) - (Ε) -3_ (3 ', 4' - dimethoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-48)

[0068] N-(1-脱氧_β -D-吡喃葡萄糖基)-(Ε)-3_(3' -硝基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-49) [0068] N- (1- deoxy _β -D- glucopyranosyl) - (Ε) -3_ (3 '- nitro - 4' - methoxy-phenyl) -2- (3 ', 4' , 5 "_ trimethoxyphenyl) acrylamide (1-49)

[0069] N-(1-脱氧_β -D-吡喃半乳糖基)-(Ε)-3_(3' -硝基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-50) [0069] N- (1- deoxy _β -D- galactopyranosyl) - (Ε) -3_ (3 '- nitro - 4' - methoxy-phenyl) -2- (3 ', 4 "5" _ trimethoxyphenyl) acrylamide (1-50)

[0070] N-(2-脱氧_β -D-吡喃葡萄糖基)-(Ε)-3_(3' -硝基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-51) [0070] N- (2- deoxy _β -D- glucopyranosyl) - (Ε) -3_ (3 '- nitro - 4' - methoxy-phenyl) -2- (3 ', 4' , 5 "_ trimethoxyphenyl) acrylamide (1-51)

[0071] N-(2-脱氧_β -D-吡喃半乳糖基)-(Ε)-3_(3' -硝基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-52) [0071] N- (2- deoxy _β -D- galactopyranosyl) - (Ε) -3_ (3 '- nitro - 4' - methoxy-phenyl) -2- (3 ', 4 "5" _ trimethoxyphenyl) acrylamide (1-52)

[0072] N-(1-脱氧-β-D-吡喃葡萄糖基)-(Ε)-3_(3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-53) [0072] N- (1- deoxy -β-D- glucopyranosyl) - (Ε) -3_ (3 '- amino-4'-methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-53)

[0073] N-(1-脱氧-β-D-吡喃半乳糖基)-(E)-3_(3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-54) [0073] N- (1- deoxy -β-D- galactopyranosyl) - (E) -3_ (3 '- amino-4'-methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-54)

[0074] N-(2-脱氧-β-D-吡喃葡萄糖基)-(E)-3_(3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-55) [0074] N- (2- deoxy -β-D- glucopyranosyl) - (E) -3_ (3 '- amino-4'-methoxyphenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-55)

[0075] N-(2-脱氧-β-D-吡喃半乳糖基)-(E)-3_(3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-56) [0075] N- (2- deoxy -β-D- galactopyranosyl) - (E) -3_ (3 '- amino-4'-methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-56)

[0076] 本发明通式化合物(I)的制备方法如下: [0076] The present invention is a compound of formula (I) are prepared as follows:

[0077] 其中关键中间体I的制备方法如下: [0077] The method of preparing the key intermediate I in which follows:

[0078] [0078]

Figure CN103421057AD00091

[0079]目标化合物(I)的制备方法如下: [0079] object compound (I) are prepared as follows:

[0080] (I)当G-NH2=G1-NH2 〜G4-NH2、G11-NH2 或G12-NH2, R=H,卤素、羟基、C1 〜C6 的烷氧 [0080] (I) when G-NH2 = G1-NH2 ~G4-NH2, G11-NH2 or G12-NH2, R = H, halogen, hydroxyl, alkoxy of C1 ~C6

基、C1〜C6的烧基、轻甲基或硝基时,合成路线如下: Group, C1~C6 burning base, when light methyl or nitro, synthetic route is as follows:

[0081] [0081]

Figure CN103421057AD00092

[0082] 反应物A为草酰氯、二氯亚砜或三乙胺/EDCI/HOBt ;溶剂A为DMF。 [0082] A reactant as oxalyl chloride, thionyl chloride or triethylamine / EDCI / HOBt; solvent A was DMF.

[0083] 其中当R=NH2时,合成路线如下: [0083] wherein when R = NH2, the synthetic route is as follows:

[0084] [0084]

Figure CN103421057AD00093

[0085] 还原剂为Fe/HCl或SnCl2 ;溶剂B为含水乙醇或含水甲醇。 [0085] the reducing agent is Fe / HCl or SnCl2; solvent B was an aqueous ethanol or aqueous methanol.

[0086] (2)当G-NH2=G5-NH2 〜Gltl-NH2 时,合成路线如下: [0086] (2) When the G-NH2 = G5-NH2 ~Gltl-NH2, synthetic route is as follows:

[0087] [0087]

Figure CN103421057AD00101

[0088] 反应物B为甲醇钠、乙醇钠或氨气;溶剂C为甲醇或乙醇。 [0088] B reactant is sodium methoxide, sodium ethoxide or ammonia; C the solvent is methanol or ethanol.

[0089] 以下是本发明部分化合物的药理试验及结果。 [0089] The following are the results of pharmacological tests and some compounds of the present invention.

[0090] 本发明部分化合物在常氧状态下对血管内皮细胞增殖抑制活性的测试方法如下: [0090] Some compounds of the present invention in 61.72 on vascular endothelial cell proliferation inhibiting activity of the test method is as follows:

[0091] 材料:人脐静脉内皮细胞(HUVEC)细胞株。 [0091] MATERIALS: Human umbilical vein endothelial cells (HUVEC) cell lines.

[0092] 溶液配制: [0092] solution preparation:

[0093] (I)PBS 溶液 [0093] (I) PBS solution

[0094] NaC18.0Og, KC10.20g, Na2HPO4.12Η203.49g,KH2PO40.20g,加三蒸水溶解后,定容至1000ml,高压灭菌后4C保存备用。 After the [0094] NaC18.0Og, KC10.20g, Na2HPO4.12Η203.49g, KH2PO40.20g, plus triple-distilled water to dissolve the volume to 1000ml, after autoclaving at 4 C for use.

[0095] (2) 0.25%胰蛋白酶溶液 [0095] (2) 0.25% trypsin solution

[0096] 称取胰蛋白酶0.25g,加入PBS溶液,磁力搅拌至完全溶解,定容至100ml,过滤除菌后一20C保存备用。 [0096] Weigh trypsin 0.25g, was added PBS solution, magnetic stirring until completely dissolved, set the volume to 100ml, sterile filtered and stored at a 20 C.

[0097] (3)噻唑兰(MTT)溶液 [0097] (3) MTT (MTT) solution

[0098] 称取MTT50mg,加入PBS使其终体积为10ml,磁力搅拌至完全溶解后,过滤除菌,4 V避光保存,两周内使用有效。 [0098] Weigh MTT50mg, PBS was added to a final volume of 10ml, magnetic stirring until completely dissolved, filter sterilized, 4 V from light, the effective use within two weeks.

[0099] 稀释方法:用二甲亚砜(DMSO)将所有被测化合物配制为浓度10_2M的母液,临用前用细胞培养液配成所需浓度。 [0099] Dilution method: with dimethyl sulfoxide (DMSO) all the test compound formulated as a concentration 10_2M mother liquor before use with cell culture medium dubbed the desired concentration.

[0100] 操作流程: [0100] flow:

[0101] 使用噻唑兰(MTT)法进行测定,主要步骤如下: [0101] The MTT assay (MTT) were measured in the following steps:

[0102] (I)取处于指数生长期状态良好的人静脉内皮细胞(HUVEC)—瓶,加入0.25%胰蛋白酶消化液,消化I〜2min,倒置显微镜下可见胞质回缩、细胞变圆、细胞间隙清晰时,立即翻转培养瓶,加入少许含10%新生牛血清的DMEM培养液终止消化,缓缓吹下瓶壁细胞,制成细胞悬液。 [0102] (I) in the exponential growth phase state to take a good human venous endothelial cells (HUVEC) - bottles, adding 0.25% trypsin digestion, digestion I~2min, visible under an inverted microscope cytoplasmic retraction, cell rounding, When clear cell gap, immediately flip flasks, adding a little of DMEM containing 10% fetal bovine serum to terminate digestion, slowly blowing down the sidewall cells, cell suspension.

[0103] (2)取细胞悬液接种于96孔板上,100 μ I/孔,每孔约5000个细胞,置恒温C02 [0103] (2) cell suspension were seeded in 96-well plates, 100 μ I / holes with approximately 5000 cells, set the thermostat C02

培养箱中培养24小时。 Incubator for 24 hours.

[0104] (3)将细胞对照组(含10%胎牛血清的DMEM)、加药组(含10%胎牛血清的DMEM和最终浓度分别为10-5mol/L、10-6ymol/L、10-7ymol/L的待检测药物),100 μ I/孔,培养24小时。 [0104] (3) The cells in the control group (containing 10% fetal bovine serum DMEM), DMEM dosing group and the final concentration (containing 10% fetal bovine serum were 10-5mol / L, 10-6ymol / L, 10-7ymol / L of the drug to be detected), 100 μ I / hole, and cultured for 24 hours.

[0105] (4)每孔加入5mg/ml 的MTT 溶液20 μ 1,37C孵育4h。 [0105] (4) was added to each well 5mg / ml of MTT solution 20 μ 1,37 C incubation 4h.

[0106] (5)吸去上清液,加入DMSO, 150 μ I/孔,平板床上振摇5分钟。 [0106] (5) Aspirate supernatant, was added DMSO, 150 μ I / aperture plates shaken for five minutes in bed.

[0107] (6)用酶联免疫检测仪在波长为570nm处测定每孔的吸光值。 [0107] (6) by enzyme-linked immunosorbent assay was measured at a wavelength at 570nm absorbance per well.

[0108] 表1.本发明部分化合物抑制人脐静脉内皮细胞(HUVEC)增殖的IC5tl(mol/L)[0109] [0108] Table 1 some compounds of the invention inhibit human umbilical vein endothelial cells (HUVEC) proliferation IC5tl (mol / L) [0109]

Figure CN103421057AD00111

[0110] 表I中化合物代号对应的化学结构同实施例。 [0110] Table I code corresponding to the chemical structure of the compound with an embodiment.

[0111] 药理测试结果表明,本发明的部分化合物,如1-1、1-3、1-6、1-9、1-25、1-29、1-30、1-31和1-34对人脐静脉内皮细胞(HUVEC)的增殖有明显的抑制作用,并且优于CA-4。 [0111] Pharmacological test results show that some compounds of the present invention, as 1-1,1-3,1-6,1-9,1-25,1-29,1-30,1-31 and 1-34 Human umbilical vein endothelial cells (HUVEC) significantly inhibited the proliferation of, and superior to CA-4.

[0112] 本发明还提供了一种治疗与血管生成相关的疾病的药物组合物,其中含有治疗有效量的通式I化合物和药学上可接受的载体。 [0112] The present invention also provides a method of treating a disease associated with angiogenesis pharmaceutical composition containing a therapeutically effective amount of a compound of formula I and a pharmaceutically acceptable carrier. 所述药物组合物可以是普通片剂或胶囊、缓释片剂或胶囊、控释片剂或胶囊、口服液、注射剂等制剂学上常规的制剂形式。 The pharmaceutical compositions may be in conventional tablets or capsules, sustained release tablets or capsules, controlled-release tablets capsules, oral liquid form preparations on conventional injection or the like pharmaceutics,.

[0113] 一般地,本发明的CA-4衍生物用于治疗时,人用剂量范围为Img〜5000mg/天。 [0113] In general, CA-4 derivative of the present invention are useful in the treatment, the human dose range of Img~5000mg / day. 也可根据剂型的不同和疾病严重程度,使用剂量超出该范围。 Can also be different depending on the severity and disease formulations, doses outside this range.

具体实施方式 DETAILED DESCRIPTION

[0114] 实施例1 [0114] Example 1

[0115] N-(2, 3,4, 6-四-O-乙酰基-1-脱氧-β _D_ 吡喃葡萄糖基)-(E) _3_ (3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-1)的制备 [0115] N- (2, 3,4, 6- four -O- -β _D_-acetyl-1-deoxy-glucopyranosyl) - (E) _3_ (3 '- hydroxy - 4' - methoxybenzene yl) -2- ("4" 5 "_ trimethoxyphenyl) acrylamide (1-1) of Preparation 3,

[0116] (E)-3-(3羟基-4' -甲氧基)苯基-2-(3”,4”,5”_三-甲氧基)苯基-丙烯酸(Ia) [0116] (E) -3- (3-hydroxy-4 '- methoxy) phenyl-2- (3', 4 ', 5' _ three - methoxy) phenyl - acrylic acid (Ia)

[0117] 在500ml三颈瓶中加入3,4,5-三甲氧基苯乙酸(50g,0.22mol)、3_羟基-4-甲氧基苯甲醛(34g,0.22mol)、62.5ml三乙胺和150ml乙酸酐,搅拌升温至140C,反应4h,停止加热,滴加浓盐酸200ml,室温下过夜。 [0117] In a three-necked 500ml flask was added 3,4,5-trimethoxy phenyl acetic acid (50g, 0.22mol), 3_-hydroxy-4-methoxybenzaldehyde (34g, 0.22mol), 62.5ml triethylamine amine and 150ml of acetic anhydride, warmed with stirring to 140 C, the reaction 4h, heating was stopped, concentrated hydrochloric acid was added dropwise 200ml, at room temperature overnight. 有土黄色固体析出,停止反应,过滤,固体用IOOml乙醇重结晶,得黄色针状物47.5g,产率为61%,mp184〜186C (文献值:184〜1860C [Bioorg.Med.Chem.,2005,13(11):3853-3864]) There khaki solid precipitation, the reaction was stopped, filtered, solid IOOml recrystallized from ethanol to give yellow needles 47.5g, a yield of 61%, mp184~186 C (literature value: 184~1860C [Bioorg.Med.Chem ., 2005,13 (11): 3853-3864])

[0118] 1Hnmr(SoomHzjDmSo), δ (ppm):12.42(m, s,⑶OH), 8.95(m, s, OH), 7.57(m, s,=CH),6.81 (1H, d, J=8.7Hz, 5,-ArH),6.61 (1H, dd, J=2.1Hz, J=8.4Hz, 6,-ArH),6.54 (1H, d,J=2.1Hz, 2' -ArH),6.44 (2H, s, 2” & 6”_ArH),3.73 (3H, s, OCH3),3.72 (3H, s, OCH3),3.69 (6H,s, 2 X OCH3).N- (2, 3, 4, 6-四-0-乙酸基-1-脱氧_ β -D-批喃匍萄糖基)- (E) -3- (3' -轻基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-1)[0119]将 G1-NH2(0.4g, 1.15mmol)溶于DMF(6ml),先后分批加入la(0.41g, 1.15mmol) [0118] 1Hnmr (SoomHzjDmSo), δ (ppm): 12.42 (m, s, ⑶OH), 8.95 (m, s, OH), 7.57 (m, s, = CH), 6.81 (1H, d, J = 8.7 Hz, 5, -ArH), 6.61 (1H, dd, J = 2.1Hz, J = 8.4Hz, 6, -ArH), 6.54 (1H, d, J = 2.1Hz, 2 '-ArH), 6.44 (2H , s, 2 "& 6" _ArH), 3.73 (3H, s, OCH3), 3.72 (3H, s, OCH3), 3.69 (6H, s, 2 X OCH3) .N- (2, 3, 4, 6 - tetra-O-acetate-1-deoxy-approved Nom creeping _ β -D- glucose group) - (E) -3- (3 '- light-4' - methoxyphenyl) -2- ( 3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-1) [0119] The G1-NH2 (0.4g, 1.15mmol) was dissolved in DMF (6ml), was added portionwise successively la (0.41 g, 1.15mmol)

,EDCI (0.22g, 1.15mmol),H0Bt(0.16g, 1.15mmol),室温搅拌24h。 , EDCI (0.22g, 1.15mmol), H0Bt (0.16g, 1.15mmol), stirred at room temperature 24h. 停止反应,用乙酸乙酯(3 X 20ml)提取,有机层依次用水(2 X 50ml)饱和食盐水(2 X 50ml)洗,无水硫酸镁干燥,过滤,减压旋除溶剂得黄色泡沫状固体0.9g,硅胶柱层析(石油醚/乙酸乙酯=2/1),得微黄色固体0.3g,收率38.2%, mp92-95C ; The reaction was stopped, and extracted with ethyl acetate (3 X 20ml), the organic layer was successively washed with water (2 X 50ml) saturated brine (2 X 50ml), dried over anhydrous magnesium sulfate, filtered, and the solvent under reduced pressure to give a spin yellow foam solid 0.9g, silica gel column chromatography (petroleum ether / ethyl acetate = 2/1) to give a slightly yellow solid 0.3g, yield 38.2%, mp92-95 C;

[0120] 1H-NmrGoomHz, CDCl3) δ (ppm):7.72 (m, s, -CH=), 6.70 〜6.62 (3Η, m, 5,-ArH, 6,-ArH&2,-ArH), 6.41 (2Η, s, 2”&6”-ArH),6.29 (1Η, d, J=9Hz, NH),5.42 (1H, brs, -ArOH),5.37 〜5.27 (2Η, m, H_l, H_2),5.05 (1H, t, J=9.6Hz, H_3),4.83 (1H, t, J=9.6Hz, H_4),4.33 (1H, dd, J=4.2Hz, J=12.3Hz, H_6a),4,13 〜4.05 (2H, m, H-6b&H_5),3.96 (3H, s, -ArOCH3),3.85 (3H, s,4”-Ar0CH3), 3.84 (6H, s, 3”&5”_Ar0CH3),2.08,2.02,1.98, 1.97 (each3H, each s, 4X0Ac); [0120] 1H-NmrGoomHz, CDCl3) δ (ppm): 7.72 (m, s, -CH =), 6.70 ~6.62 (3Η, m, 5, -ArH, 6, -ArH & 2, -ArH), 6.41 (2Η , s, 2 "& 6" -ArH), 6.29 (1Η, d, J = 9Hz, NH), 5.42 (1H, brs, -ArOH), 5.37 ~5.27 (2Η, m, H_l, H_2), 5.05 (1H , t, J = 9.6Hz, H_3), 4.83 (1H, t, J = 9.6Hz, H_4), 4.33 (1H, dd, J = 4.2Hz, J = 12.3Hz, H_6a), 4,13 ~4.05 ( 2H, m, H-6b & H_5), 3.96 (3H, s, -ArOCH3), 3.85 (3H, s, 4 "-Ar0CH3), 3.84 (6H, s, 3" & 5 "_Ar0CH3), 2.08,2.02,1.98, 1.97 (each3H, each s, 4X0Ac);

[0121] IR(cm_1): 3404 (OH),2944 (CH),1751 (ester, C=O), 1670 (amide, C=O), 1581,1511,I234 (OCH3), 1127 (OAc),1038 (OCH3) [0121] IR (cm_1): 3404 (OH), 2944 (CH), 1751 (ester, C = O), 1670 (amide, C = O), 1581,1511, I234 (OCH3), 1127 (OAc), 1038 (OCH3)

[0122] MS (ESI(+)70eV, m/z): 690.2 [M+H]+; MS (ESI (-) 70V, m/z): 724.4 [M+C1F; [0122] MS (ESI (+) 70eV, m / z): 690.2 [M + H] +; MS (ESI (-) 70V, m / z): 724.4 [M + C1F;

[0123] HR-MS (1: TOF MS ES (+)5.96e4):Calc.Mass:712.2217, C33H39NO15Na.FoundMass: 712.2223.[0124] 实施例2 [0123] HR-MS (1: TOF MS ES (+) 5.96e4): Calc.Mass: 712.2217, C33H39NO15Na.FoundMass:. 712.2223 [0124] Example 2

[0125] N-(2, 3,4, 6-四_0_ 乙酰基-1-脱氧-β _D_ 吡喃半乳糖基)-(E) _3_ (3' -羟基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-2)的制备 [0125] N- (2, 3,4, 6- four _0_ -β _D_-acetyl-1-deoxy-galactopyranosyl) - (E) _3_ (3 '- hydroxy-4'-methoxyphenoxy yl) -2- ("4" 5 "_ trimethoxyphenyl) acrylamide (1-2) of Preparation 3,

[0126]将 G2-NH2 (0.4g, 1.15mmol), la (0.41g, 1.15mmol)经同I_1 操作得微黄色固体0.32g,收率40.8%, mp118-120C ; [0126] The G2-NH2 (0.4g, 1.15mmol), la (0.41g, 1.15mmol) obtained by operating with I_1 slightly yellow solid 0.32g, yield 40.8%, mp118-120 C;

[0127] 1H-匪R(300MHz,. CDCl3) δ (ppm):7.73 (1Η, s, -CH=), 6.66 〜6.61 (3Η, m, 5' -ArH, 6,-ArH&2,-ArH),6.42 (2Η, s, 2” &6” -ArH),6.29 (1Η, d, J=9.6Hz, NH),5.43 (1Η, brs,-ArOH), 5.42(1Η, s, Η-4), 5.34(1Η, t, J=9.3Hz, Hl), 5.12 〜5.11 (1Η, m, Η_2),5.01 〜4.98 (1Η, m, Η_3),4.13 〜4.09 (3Η, m, Η_5, H_6a and H_6b),3.97 (3Η, s, 4,_Ar0CH3),3.85 (9H, s, 4”-ArOCH3,3”&5”-ArOCH3),2.14,2.04,1.99,1.98 (each3H, each s, 4X0Ac); [0127] 1H- bandit R (300MHz ,. CDCl3) δ (ppm): 7.73 (1Η, s, -CH =), 6.66 ~6.61 (3Η, m, 5 '-ArH, 6, -ArH & 2, -ArH) , 6.42 (2Η, s, 2 "& 6" -ArH), 6.29 (1Η, d, J = 9.6Hz, NH), 5.43 (1Η, brs, -ArOH), 5.42 (1Η, s, Η-4), 5.34 (1Η, t, J = 9.3Hz, Hl), 5.12 ~5.11 (1Η, m, Η_2), 5.01 ~4.98 (1Η, m, Η_3), 4.13 ~4.09 (3Η, m, Η_5, H_6a and H_6b) , 3.97 (3Η, s, 4, _Ar0CH3), 3.85 (9H, s, 4 "-ArOCH3,3" & 5 "-ArOCH3), 2.14,2.04,1.99,1.98 (each3H, each s, 4X0Ac);

[0128] IR(cm_1): 3407 (OH),2941 (CH),1750 (ester, C=0), 1677 (amide, C=0), 1581,1509,I229 (OCH3), 1126 (OAc), 1082 (OCH3), 1051 [0128] IR (cm_1): 3407 (OH), 2941 (CH), 1750 (ester, C = 0), 1677 (amide, C = 0), 1581,1509, I229 (OCH3), 1126 (OAc), 1082 (OCH3), 1051

[0129] MS (ESI (+) 70eV, m/z): 690.2 [M+H] +; MS (ESI (-) 70V, m/z): 688.0 [M_H] ^; [0129] MS (ESI (+) 70eV, m / z): 690.2 [M + H] +; MS (ESI (-) 70V, m / z): 688.0 [M_H] ^;

[0130] HR-MS (1: TOF MS ES (+) 5.85e3): Calc.Mass: 712.2217,C33H39N015Na.FoundMass: 712.2221.[0131] 实施例3 [0130] HR-MS (1: TOF MS ES (+) 5.85e3): Calc.Mass: 712.2217, C33H39N015Na.FoundMass:. 712.2221 [0131] Example 3

[0132] N-(l,3,4,6-四_0_ 乙酰基_2_ 脱氧-β _D_ 吡喃葡萄糖基)-(E) _3_(3,-羟基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-3)的制备 [0132] N- (l, 3,4,6- four _0_ acetyl -β _D_ _2_ deoxy-glucopyranosyl) - (E) _3_ (3, - hydroxy-4'-methoxyphenyl) 2- ("4" 5 "_ trimethoxyphenyl 3) acrylamide (1-3) Preparation of

[0133]将 G3-NH2.HCl (1.15g, 3mmol)溶于DMF (12ml),滴加三乙胺(0.42ml, 3mmol)。 [0133] The G3-NH2.HCl (1.15g, 3mmol) was dissolved in DMF (12ml), triethylamine (0.42ml, 3mmol). 先后分批加入Ia (1.08g, 3mmol),EDCI (0.58g, 3mmol),HOBt (0.41g, 3mmol),室温搅拌24h。 Successively portionwise added Ia (1.08g, 3mmol), EDCI (0.58g, 3mmol), HOBt (0.41g, 3mmol), stirred at room temperature 24h. 反应液加入二氯甲烷(80ml),水洗(2X 100ml),饱和食盐水洗(3X 100ml),无水硫酸镁干燥,抽滤,减压蒸除溶剂,得黄色糖浆状粗品2g,硅胶柱层析(石油醚/乙酸乙酯=1/1),得白色固体0.39g,收率18.9%, mp78-80C ; The reaction solution was added dichloromethane (80ml), washed with water (2X 100ml), brine (3X 100ml), dried over anhydrous magnesium sulfate, suction filtered, the solvent evaporated under reduced pressure to give a yellow syrupy crude 2g, silica gel column chromatography (petroleum ether / ethyl acetate = 1/1) to give a white solid 0.39g, yield 18.9%, mp78-80 C;

[0134] 1H-NMR (300MHz, CDCl3) δ (ppm): 7.70 ( IH, s , -CH = ) , 6.68 〜6.65 (1H, m, 5'_ArH), 6.60 〜6.58 (2H,m, 6'-ArH&2'_ArH),6.33 (2H, s, 2”&6”_ArH),5.66(1H, d, J=8.7Hz, NH), 5.51 (1H, d, J=9.6Hz, Hl), 5.17 — 5.02 (2H, m, H_3, H_4),4.44 〜4.35 (1H,m, H-2),4.26 (1H, dd, J=4.6Hz, J=12.5Hz, H_6a),4.16 (1H, brs, -ArOH), 4.13 — 4.09 (1H, m,H-6b),3.96 (3H, s, 4' -ArOCH3),3.85 (3H, s, 4”_ArOCH3),3.83 (6H, s, 3 ”&5 ”_ArOCH3),3.77 〜 [0134] 1H-NMR (300MHz, CDCl3) δ (ppm): 7.70 (IH, s, -CH =), 6.68 ~6.65 (1H, m, 5'_ArH), 6.60 ~6.58 (2H, m, 6 ' -ArH & 2'_ArH), 6.33 (2H, s, 2 "& 6" _ArH), 5.66 (1H, d, J = 8.7Hz, NH), 5.51 (1H, d, J = 9.6Hz, Hl), 5.17 - 5.02 (2H, m, H_3, H_4), 4.44 ~4.35 (1H, m, H-2), 4.26 (1H, dd, J = 4.6Hz, J = 12.5Hz, H_6a), 4.16 (1H, brs, -ArOH ), 4.13 - 4.09 (1H, m, H-6b), 3.96 (3H, s, 4 '-ArOCH3), 3.85 (3H, s, 4 "_ArOCH3), 3.83 (6H, s, 3" & 5 "_ArOCH3) 3.77 ~

3.74 (1H, m, H_5), 2.10, 2.09, 2.01, 2.0O (each3H, each s, 4 X OAc); 3.74 (1H, m, H_5), 2.10, 2.09, 2.01, 2.0O (each3H, each s, 4 X OAc);

[0135] IR(cm_1): 3400 (OH),2941 (CH),1753 (ester, C=O), 1665 (amide, C=O), 1581,1512,I234 (OCH3), 1127 (OAc),1038 (OCH3) [0135] IR (cm_1): 3400 (OH), 2941 (CH), 1753 (ester, C = O), 1665 (amide, C = O), 1581,1512, I234 (OCH3), 1127 (OAc), 1038 (OCH3)

[0136] MS (ESI (-) 70V, m/z): 688.0 [M_H] ^; [0136] MS (ESI (-) 70V, m / z): 688.0 [M_H] ^;

[0137] HR-MS (1: TOF MS ES (-) 6.50e3): Calc.Mass: 688.2241,C33H38NO15.FoundMass: 688.2245.[0138] 实施例4 [0137] HR-MS (1: TOF MS ES (-) 6.50e3):. Calc.Mass: 688.2241, C33H38NO15.FoundMass: 688.2245 [0138] Example 4

[0139] N-(2,3,4,6-四_0_乙酰基_1_脱氧-β _D_吡喃葡萄糖基)-(E)-3_(4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-5)的制备 [0139] N- (2,3,4,6- four _0_ acetyl -β _D_ _1_ deoxy-glucopyranosyl) - (E) -3_ (4'- methoxyphenyl) - 2- ("4" 5 "_ trimethoxyphenyl 3) acrylamide (1-5) Preparation of

[0140] (E)-3-(4,-甲氧基)苯基-2-(3”,4”,5”_三甲氧基)苯基-丙烯酸(Ib) [0140] (E) -3- (4, - methoxy) phenyl-2- (3 ', 4', 5 '_ trimethoxy) phenyl - acrylic acid (Ib)

[0141] 在500ml三颈瓶中加入3,4, 5_三甲氧基苯乙酸(IOg, 44.2mmol)、4_甲氧基苯甲醛(5.4ml, 44.2mmol)、IOml三乙胺和IOOml乙酸酐,搅拌升温至140C,反应20h,停止加热,滴加浓盐酸60ml,室温下过夜。 [0141] In a three-necked 500ml flask was added 3,4, 5_ trimethoxy acid (IOg, 44.2mmol), 4_-methoxybenzaldehyde (5.4ml, 44.2mmol), IOml triethylamine and acetic IOOml anhydride, stirring was heated to 140 C, the reaction 20h, heating was stopped, concentrated hydrochloric acid was added dropwise 60ml, at room temperature overnight. 有土黄色固体析出,停止反应过滤出固体,用约IOOml乙醇重结晶,得黄色针状物4.4g,产率为28.9%,mp209〜21 TC (文献值:212C [Bioorg.Med.Chem.,2005,13(11):3853 〜3864.]) There khaki solid precipitated solid was filtered off to stop the reaction, with about IOOml recrystallized from ethanol to give yellow needles 4.4g, yield 28.9%, mp209~21 TC (literature value: 212 C [Bioorg.Med.Chem ., 2005,13 (11): 3853 ~3864]).

[0142] N-(2,3,4,6-四_0_乙酰基_1_脱氧-β-D-吡喃葡萄糖基)-(E)-3_(4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-5).[0143] G1-NH2 (0.9g, 2.6mmol), Ib (0.9g, 2.6mmol)经同1-1 操作得淡黄色固体0.8g,收率45.4%, mp83-85 C ; [0142] N- (2,3,4,6- four _0_ acetyl _1_ deoxy -β-D- glucopyranosyl) - (E) -3_ (4'- methoxyphenyl) 2- (3 ', 4', 5 '_ trimethoxyphenyl) acrylamide (1-5). [0143] G1-NH2 (0.9g, 2.6mmol), Ib (0.9g, 2.6mmol) by 1-1 operate with light yellow solid 0.8g, yield 45.4%, mp83-85 C;

[0144] 1H-MffiOOOMHz, CDCl3) δ (ppm):7.78 (1H, s, -CH=), 7.00 (2Η, d, J=8.8Hz, 2,-ArH,6'-ArH),6.71 (2Η, d, J=8.8Hz, 3'_ArH, 5'_ArH),6.41 (2H, s, 2”&6”_ArH),6.29 (1H, d, J=9Hz, NH), 5.38 — 5.27 (2H, m, Hl, H-2),5.05 (1H, t, J=9.7Hz, H_3),4.84 (1H, t, J=9.5Hz, H_4),4.34 (1H, dd, J=4.1Hz, J=12.5Hz, H_6a),4.10 〜4.06 (1H, m, H_6b),3.96 (3H, s, 4”_Ar0CH3),3.87 (1H, m, H-5),3.84 (6H, s, 3 ”&5 ”_Ar0CH3),3.77 (3H, s, 4' -ArOCH3),2.08,2.02 (each3H, eachs, 2 X OAc),1.98,(6H, s, 2 X OAc); [0144] 1H-MffiOOOMHz, CDCl3) δ (ppm): 7.78 (1H, s, -CH =), 7.00 (2Η, d, J = 8.8Hz, 2, -ArH, 6'-ArH), 6.71 (2Η , d, J = 8.8Hz, 3'_ArH, 5'_ArH), 6.41 (2H, s, 2 "& 6" _ArH), 6.29 (1H, d, J = 9Hz, NH), 5.38 - 5.27 (2H, m , Hl, H-2), 5.05 (1H, t, J = 9.7Hz, H_3), 4.84 (1H, t, J = 9.5Hz, H_4), 4.34 (1H, dd, J = 4.1Hz, J = 12.5 Hz, H_6a), 4.10 ~4.06 (1H, m, H_6b), 3.96 (3H, s, 4 "_Ar0CH3), 3.87 (1H, m, H-5), 3.84 (6H, s, 3" & 5 "_Ar0CH3) , 3.77 (3H, s, 4 '-ArOCH3), 2.08,2.02 (each3H, eachs, 2 X OAc), 1.98, (6H, s, 2 X OAc);

[0145] IR(cm_1):2941 (CH),1751 (ester, C=0), 1676 (amide, C=0), 1603,1513,1384,1236 (OCH3), 1127 (OAc),1037 (OCH3) [0145] IR (cm_1): 2941 (CH), 1751 (ester, C = 0), 1676 (amide, C = 0), 1603,1513,1384,1236 (OCH3), 1127 (OAc), 1037 (OCH3 )

[0146] MS (ESI (+) 70eV, m/z): 674.3 [M+H] +; [0146] MS (ESI (+) 70eV, m / z): 674.3 [M + H] +;

[0147] HR-MS (1: TOF MS ES (+) 7.22e3): Calc.Mass: 696.2268, C33H39NO14Na.FoundMass: 696.2272.[0148] 实施例5 [0147] HR-MS (1: TOF MS ES (+) 7.22e3): Calc.Mass: 696.2268, C33H39NO14Na.FoundMass:. 696.2272 [0148] Example 5

[0149] N-(2,3,4,6-四_0_乙酰基_1_脱氧-β _D_吡喃半乳糖基)-(E)-3_(4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-6)的制备 [0149] N- (2,3,4,6- four _0_ acetyl -β _D_ _1_ deoxy-galactopyranosyl) - (E) -3_ (4'- methoxyphenyl) 2- ("4" 5 "_ trimethoxyphenyl 3) acrylamide (1-6) Preparation of

[0150] G2-NH2 (0.9g, 2.6mmol),Ib (0.9g, 2.6mmol)经同1-1 操作得淡黄色固体0.6g,收率34.1%,mp76-78 0C ;[0151] 1H-NMR (300MHz, CDCl3) δ (ppm):7.78 (1H, s, -CH=), 7.00 (2H, d, J=8.8Hz, 2,-ArH, 6'-ArH),6.71 (2H, d, J=8.9Hz, 3'_ArH, 5'_ArH),6.43 (2H, s, 2”&6”-ArH),6.29 (1H, d, J=9.3Hz, NH),5.43 (1H, d, J=3.4Hz, H_4),5.35 (1H, t, J=9.3Hz, Hl),5.14 (1H, dd, J=3.5Hz, J=I0.3Hz,H-3),4.98 (1H, t, J=9.5Hz, H-2), 4.13 — 4.07 (3H, m, H-5, H-6a&H_6b),3.98 (3H, s, 4 ^-ArOCH3),3.85 (6H, s, 3”&5”-Ar0CH3), 3.77 (3H, s, 4'-ArOCH3),2.14,2.04,1.99,1.96 (each3H, eachs, 4 X OAc); [0150] G2-NH2 (0.9g, 2.6mmol), Ib (0.9g, 2.6mmol) by the same operation was 1-1 as a pale yellow solid 0.6g, yield 34.1%, mp76-78 0C; [0151] 1H- NMR (300MHz, CDCl3) δ (ppm): 7.78 (1H, s, -CH =), 7.00 (2H, d, J = 8.8Hz, 2, -ArH, 6'-ArH), 6.71 (2H, d, J = 8.9Hz, 3'_ArH, 5'_ArH), 6.43 (2H, s, 2 "& 6" -ArH), 6.29 (1H, d, J = 9.3Hz, NH), 5.43 (1H, d, J = 3.4Hz, H_4), 5.35 (1H, t, J = 9.3Hz, Hl), 5.14 (1H, dd, J = 3.5Hz, J = I0.3Hz, H-3), 4.98 (1H, t, J = 9.5Hz, H-2), 4.13 - 4.07 (3H, m, H-5, H-6a & H_6b), 3.98 (3H, s, 4 ^ -ArOCH3), 3.85 (6H, s, 3 "& 5" -Ar0CH3) , 3.77 (3H, s, 4'-ArOCH3), 2.14,2.04,1.99,1.96 (each3H, eachs, 4 X OAc);

[0152] IR(cm_1):2936 (CH),1750 (ester, C=O), 1679 (amide, C=O), 1603,1513,1371,1231 (OCH3), 1177,1127 (OAc), 1052 (OCH3),910 [0152] IR (cm_1): 2936 (CH), 1750 (ester, C = O), 1679 (amide, C = O), 1603,1513,1371,1231 (OCH3), 1177,1127 (OAc), 1052 (OCH3), 910

[0153] MS (ESI (+) 70eV, m/z): 674.2 [M+H] +; [0153] MS (ESI (+) 70eV, m / z): 674.2 [M + H] +;

[0154] HR-MS (1: TOF MS ES (+) 7.64e3): Calc.Mass: 696.2268, C33H39NO14Na.FoundMass: 696.2273.[0155] 实施例6 [0154] HR-MS (1: TOF MS ES (+) 7.64e3): Calc.Mass: 696.2268, C33H39NO14Na.FoundMass:. 696.2273 [0155] Example 6

[0156] N-(2,3,4,6_四_0_乙酰基-1-脱氧-β _D_吡喃葡萄糖基)-(E)-3-(3' -氯-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_9)的制备 [0156] N- (2,3,4,6_ four _0_ -β _D_-acetyl-1-deoxy-glucopyranosyl) - (E) -3- (3 '- chloro-4' - methyl methoxyphenyl) -2- ("4" 5 "_ trimethoxyphenyl) acrylamide (1_9) of Preparation 3,

[0157] (E)-3-(3,-氯-4' -甲氧基)苯基_ 2_ (3”,4”,5” -三甲氧基)苯基-丙烯酸(Ic) [0157] (E) -3- (3, - chloro-4 '- methoxy) phenyl 2_ _ (3 ", 4", 5 "- trimethoxy) phenyl - acrylic acid (Ic)

[0158] 在250ml三颈瓶中加入3,4,5-三甲氧基苯乙酸(13.3g,58.8mmol)、3_氯-4-甲氧基苯甲醒(5g, 29.3mmol) > 13.3ml三乙胺和26.6ml乙酸酐,搅拌升温至140C,反应18h,停止加热,滴加浓盐酸40ml,室温下过夜。 [0158] In a three-necked 250ml flask was added 3,4,5-trimethoxy phenyl acetic acid (13.3g, 58.8mmol), 3_-chloro-4-methoxy-benzoic awake (5g, 29.3mmol)> 13.3ml 26.6ml of triethylamine and acetic anhydride, heated with stirring to 140 C, the reaction 18h, heating was stopped, concentrated hydrochloric acid was added dropwise 40ml, at room temperature overnight. 有土黄色固体析出,停止反应,过滤,固体用约IOOml乙醇重结晶,得黄色针状物7.0g,产率为63.1%,mp208〜210。 There khaki solid precipitation, to stop the reaction, filtered and the solids with about IOOml recrystallized from ethanol to give yellow needles 7.0g, yield 63.1%, mp208~210. . .

[0159] 1Hnmr(SoomHzjDmSo-CI6), δ (ppm):7.64(m, S,=CH), 7.1l 〜7.09(2H,m, 6,&2,-ArH),7.04 (1H, d, J=9.3Hz, 5' -ArH),6.47 (2H, s, 2”& 6”_ArH),3.82 (3H, s, 4' -ArOCH3), 3.71(3H, s, 4” -ArOCH3),3.69 (6H, s, 3” &5” -ArOCH3).[0160] N-(2, 3, 4, 6-四_0_乙酰基-1-脱氧-β _D_吡喃葡萄糖基)-(E) -3- (3' -氯-4' -甲氧基苯基)-2- (3”,4”,5” -三甲氧基苯基)丙烯酰胺(1_9) [0159] 1Hnmr (SoomHzjDmSo-CI6), δ (ppm): 7.64 (m, S, = CH), 7.1l ~7.09 (2H, m, 6, & 2, -ArH), 7.04 (1H, d, J = 9.3Hz, 5 '-ArH), 6.47 (2H, s, 2 "& 6" _ArH), 3.82 (3H, s, 4' -ArOCH3), 3.71 (3H, s, 4 "-ArOCH3), 3.69 (6H , s, 3 "& 5" -ArOCH3) [0160] N- (2, 3, 4, 6- four _0_ -β _D_-acetyl-1-deoxy-glucopyranosyl) -. (E) -3 - (3 '- chloro-4' - methoxy-phenyl) -2- (3 ", 4", 5 "- trimethoxyphenyl) acrylamide (1_9)

[0161] G1-NH2 (0.9g, 2.6mmol),Ic (0.98g, 2.6mmol))经同I_1 操作得淡黄色固体0.7g,收率38.2%, mp69-72 0C ; [0161] G1-NH2 (0.9g, 2.6mmol), Ic (0.98g, 2.6mmol)) obtained by the same operation as a pale yellow solid I_1 0.7g, yield 38.2%, mp69-72 0C;

[0162] 1H-NMR (500MHz, CDCl3) δ (ppm):7.69 (1H, s, -CH=), 7.05 (1Η, d, J=2.15Hz, 2,-ArH) [0162] 1H-NMR (500MHz, CDCl3) δ (ppm): 7.69 (1H, s, -CH =), 7.05 (1Η, d, J = 2.15Hz, 2, -ArH)

,6.91 (1Η, dd, J=2.15Hz, J=8.7Hz, 6'_ArH),6.72 (1Η, d, J=8.7Hz, 5'_ArH),6.40 (2H, s, 2,,&6,,_ArH),6.32 (1H, d, J=9.2Hz, NH), 5.36 — 5.28 (2H, m, Hl, H-2),5.04 (1H, t, J=9.6Hz, H-3),4.83 (1H, t, J=9.6Hz, H_4),4.32 (1H, dd, J=4.3Hz, J=12.5Hz, H_6a),4,14 〜4.09 (2H, m, H_6b&H-5),3.96 (3H, s, 4'-ArOCH3),3.85 (3H, s, 4”_Ar0CH3),3.84 (6H, s, 3 ”&5 ”_ArOCH3),2.07,2.04,2.02, 1.98 (each3H, each s, 4 X OAc); , 6.91 (1Η, dd, J = 2.15Hz, J = 8.7Hz, 6'_ArH), 6.72 (1Η, d, J = 8.7Hz, 5'_ArH), 6.40 (2H, s, 2 ,, & 6 ,, _ArH), 6.32 (1H, d, J = 9.2Hz, NH), 5.36 - 5.28 (2H, m, Hl, H-2), 5.04 (1H, t, J = 9.6Hz, H-3), 4.83 ( 1H, t, J = 9.6Hz, H_4), 4.32 (1H, dd, J = 4.3Hz, J = 12.5Hz, H_6a), 4,14 ~4.09 (2H, m, H_6b & H-5), 3.96 (3H, s, 4'-ArOCH3), 3.85 (3H, s, 4 "_Ar0CH3), 3.84 (6H, s, 3" & 5 "_ArOCH3), 2.07,2.04,2.02, 1.98 (each3H, each s, 4 X OAc);

[0163] IR (cm-1): 2943 (CH),1752 (ester, C=O),1678 (amide, C=O),1596,1505,1372,1236 (OCH3), 1127 (OAc),1064 (ArCl),1038 (OCH3); [0163] IR (cm-1): 2943 (CH), 1752 (ester, C = O), 1678 (amide, C = O), 1596,1505,1372,1236 (OCH3), 1127 (OAc), 1064 (ArCl), 1038 (OCH3);

[0164] MS (ESI(+)70eV, m/z): 708.2 [M+H]+; MS (ESI (-) 70V, m/z): 742.6 [M+C1F; [0164] MS (ESI (+) 70eV, m / z): 708.2 [M + H] +; MS (ESI (-) 70V, m / z): 742.6 [M + C1F;

[0165] HR-MS (1: TOF MS ES (+) 7.99e3): Calc.Mass: 730.1879, C33H38NO14NaCl.FoundMass: 730.1884.[0166] 实施例7 [0165] HR-MS (1: TOF MS ES (+) 7.99e3): Calc.Mass: 730.1879, C33H38NO14NaCl.FoundMass:. 730.1884 [0166] Example 7

[0167] N-(2,3,4,6_四-O-乙酰基-1-脱氧-β-D-吡喃半乳糖基)-(Ε)-3-(3'_氯-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1_10)的制备 [0167] N- (2,3,4,6_ four -O- acetyl-1-deoxy -β-D- galactopyranosyl) - (Ε) -3- (3'_ chloro-4 ' - methoxyphenyl) -2- (3 ", 4" 5 "_ trimethoxyphenyl) acrylamide (1_10) the preparation,

[0168]将 G2-NH2 (0.9g, 2.Bmmol), Ic (0.98g, 2.Bmmol)经同1-1 操作得白色固体0.6g,收率32.8%, mp93-95 0C ; [0168] The G2-NH2 (0.9g, 2.Bmmol), Ic (0.98g, 2.Bmmol) by the same 1-1 operate as a white solid 0.6g, yield 32.8%, mp93-95 0C;

[0169] 1H-NMR (500MHz, CDCl3) δ (ppm):7.70 (1H, s, -CH=), 7.03 (1Η, d, J=2.15Hz, 2,-ArH) [0169] 1H-NMR (500MHz, CDCl3) δ (ppm): 7.70 (1H, s, -CH =), 7.03 (1Η, d, J = 2.15Hz, 2, -ArH)

,6.93 (1Η, dd, J=2.15Hz, J=8.75Hz, 6'_ArH), 6.73 (1Η, d, J=8.7Hz, 5'_ArH), 6.42 (2Η, s, 2”&6”-ArH),6.33 (1Η, d, J=9.25Hz, NH),5.43 (1Η, d, J=3.5Ηζ, Η-4),5.35 (1Η, t, J=9.3Ηζ, Η_1),5.14 (1Η, dd, J=3.5Hz, J=I0.3Ηζ, Η_3),4.98 (1Η, t, J=9.55Ηζ, Η_2),4,14 〜4.09 (3Η, m, Η_5, Η_6a&H-6b),3.97 (3Η, s, 4'-ArOCH3),3.86 (9Η, s, 4”_Ar0CH3,3”&5 ”_ArOCH3),2.14,2.04,2.00,1.96 (each3H, each s, 4 X OAc); , 6.93 (1Η, dd, J = 2.15Hz, J = 8.75Hz, 6'_ArH), 6.73 (1Η, d, J = 8.7Hz, 5'_ArH), 6.42 (2Η, s, 2 "& 6" -ArH ), 6.33 (1Η, d, J = 9.25Hz, NH), 5.43 (1Η, d, J = 3.5Ηζ, Η-4), 5.35 (1Η, t, J = 9.3Ηζ, Η_1), 5.14 (1Η, dd, J = 3.5Hz, J = I0.3Ηζ, Η_3), 4.98 (1Η, t, J = 9.55Ηζ, Η_2), 4,14 ~4.09 (3Η, m, Η_5, Η_6a & H-6b), 3.97 (3Η , s, 4'-ArOCH3), 3.86 (9Η, s, 4 "_Ar0CH3,3" & 5 "_ArOCH3), 2.14,2.04,2.00,1.96 (each3H, each s, 4 X OAc);

[0170] IR(cm_1):2941 (CH),1748 (ester, C=O), 1682 (amide, C=O), 1596,1505,1371,1234(OCH3), 1127 (OAc),1082 (ArCl),1063 (OCH3) [0170] IR (cm_1): 2941 (CH), 1748 (ester, C = O), 1682 (amide, C = O), 1596,1505,1371,1234 (OCH3), 1127 (OAc), 1082 (ArCl ), 1063 (OCH3)

[0171] MS (ESI(+)70eV, m/z): 708.2 [M+H]+; MS (ESI (-) 70V, m/z): 742.6 [M+C1F; [0171] MS (ESI (+) 70eV, m / z): 708.2 [M + H] +; MS (ESI (-) 70V, m / z): 742.6 [M + C1F;

[0172] HR-MS (1: TOF MS ES (+) 3.10e4): Calc.Mass: 730.1879, C33H38NO14NaCl.FoundMass: 730.1883.[0173] 实施例8 [0172] HR-MS (1: TOF MS ES (+) 3.10e4): Calc.Mass: 730.1879, C33H38NO14NaCl.FoundMass:. 730.1883 [0173] Example 8

[0174] N-(l,3,4,6-四_0_乙酰基_2_脱氧-β _D_吡喃葡萄糖基)-(E)-3-(3'_氯-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-1l)的制备 [0174] N- (l, 3,4,6- four _0_ acetyl -β _D_ _2_ deoxy-glucopyranosyl) - (E) -3- (3'_ chloro-4'-methyl methoxyphenyl) -2- ("4" 5 "_ trimethoxyphenyl) acrylamide (1-1l) Preparation of 3,

[0175] G3-NH2.HCl (1. 15g, 3mmol),Ic (1.2g, 3mmol)经同1-3 操作得白色固体0.6g,收率26.7%, mp119-121 C ; [0175] G3-NH2.HCl (1. 15g, 3mmol), Ic (1.2g, 3mmol) by the same 1-3 operate as a white solid 0.6g, yield 26.7%, mp119-121 C;

[0176] 1H-NMR (500MHz, CDCl3) δ (ppm):7.67 (1H, s, -CH=), 7.005 (1H, d, J=2.2Hz, 2,-ArH),6.89(1H, dd, J=2.2Hz, J=8.7Hz, 6'_ArH), 6.72(1H, d, J=8.7Hz, 5'_ArH), 6.33(2H, s, 2”&6”_ArH),5.67 (1H, d, J=8.6Hz, NH),5.57 (1H, d, J=9.6Hz, Hl),5.14 (1H, t, J=9.4Hz, H-3),5.06 (1H, dd, J=9.3Hz, J=I0.35Hz, H_4),4.38 (1H, t, J=9.4Hz, H-2),4.26 (1H, dd, J=4.7Hz, J=I [0176] 1H-NMR (500MHz, CDCl3) δ (ppm): 7.67 (1H, s, -CH =), 7.005 (1H, d, J = 2.2Hz, 2, -ArH), 6.89 (1H, dd, J = 2.2Hz, J = 8.7Hz, 6'_ArH), 6.72 (1H, d, J = 8.7Hz, 5'_ArH), 6.33 (2H, s, 2 "& 6" _ArH), 5.67 (1H, d, J = 8.6Hz, NH), 5.57 (1H, d, J = 9.6Hz, Hl), 5.14 (1H, t, J = 9.4Hz, H-3), 5.06 (1H, dd, J = 9.3Hz, J = I0.35Hz, H_4), 4.38 (1H, t, J = 9.4Hz, H-2), 4.26 (1H, dd, J = 4.7Hz, J = I

2.45Hz, H-6a),4,13 〜4.10 (1H, m, H_6b),3.96 (3H, s, 4' -ArOCH3),3.85 (3H, s, 4” -ArOCH3) 2.45Hz, H-6a), 4,13 ~4.10 (1H, m, H_6b), 3.96 (3H, s, 4 '-ArOCH3), 3.85 (3H, s, 4 "-ArOCH3)

,3.84 (6H, s, 3,,&5”-ArOCH3),3.78 〜3.75 (1H, m, H-5), 2.11, 2.09, 2.01, 2.00 (each3H, eachs, 4 X OAc); , 3.84 (6H, s, 3 ,, & 5 "-ArOCH3), 3.78 ~3.75 (1H, m, H-5), 2.11, 2.09, 2.01, 2.00 (each3H, eachs, 4 X OAc);

[0177] IR(cm_1):2939 (CH),1751 (ester, C=O), 1673 (amide, C=O), 1597,1504,1368,1233(OCH3),1128 (OAc),1077 (ArCl),1041 (OCH3) [0177] IR (cm_1): 2939 (CH), 1751 (ester, C = O), 1673 (amide, C = O), 1597,1504,1368,1233 (OCH3), 1128 (OAc), 1077 (ArCl ), 1041 (OCH3)

[0178] MS (ESI (-) 70V, m/z): 742.6 [M+C1F ; [0178] MS (ESI (-) 70V, m / z): 742.6 [M + C1F;

[0179] HR-MS (1: TOF MS ES (+) 1.61e4): Calc.Mass: 730.1879,C33H38NO14NaCl.FoundMass: 730.1884.[0180] 实施例9 [0179] HR-MS (1: TOF MS ES (+) 1.61e4): Calc.Mass: 730.1879, C33H38NO14NaCl.FoundMass:. 730.1884 [0180] Example 9

[0181] N-(2,3,4,6-四_0_ 乙酰基-1-脱氧-β _D_ 吡喃葡萄糖基)-(E) _3_ (3',4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-17)的制备 [0181] N- (2,3,4,6- four _0_ -β _D_-acetyl-1-deoxy-glucopyranosyl) - (E) _3_ (3 ', 4' - dimethoxyphenyl) 2- ("4" 5 "_ trimethoxyphenyl 3) acrylamide (1-17) was prepared

[0182] (E)-3-(3',4'_ 二甲氧基)苯基-2_(3”,4”,5”-三甲氧基)苯基-丙烯酸(Ie)[0183] 在250ml三颈瓶中加入3,4,5-三甲氧基苯乙酸(5g,22.lmmol)、3,4_ 二甲氧基苯甲醛(3.7g, 22.lmmol)、5ml三乙胺和50ml乙酸酐,搅拌升温至140C,反应20h,停止加热,滴加浓盐酸30ml,室温下过夜。有土黄色固体析出,停止反应,过滤,固体用约80ml乙醇重结晶,得黄色针状物纯品3g,产率为36.3%,mp205_208C。 [0182] (E) -3- (3 ', 4'_ dimethoxy) phenyl -2_ (3 ", 4", 5 "- trimethoxy) phenyl - acrylate (Ie) [0183] In 250ml three-necked flask was added 3,4,5-trimethoxy phenyl acetic acid (5g, 22.lmmol), 3,4_-dimethoxybenzaldehyde (3.7g, 22.lmmol), 5ml of triethylamine and 50ml of ethyl anhydride, stirring heated to 140 C, the reaction 20h, stop heating, dropping concentrated hydrochloric acid 30ml, at room temperature overnight. There khaki solid precipitation, to stop the reaction, filtered and the solids with about 80ml recrystallized from ethanol to give yellow needles of pure product 3g, yield 36.3%, mp205_208 C.

[0184] 1HNMR (300MHz, DMS0_d6),δ (ppm):12.45 (1Η, brs, C00H),7.67 (1Η, s, =CH),6.88 (2H, s, 2,&6,-ArH), 6.54 (1H, s, 5,_ArH), 6.49 (2H, s, 2,,& 6”_ArH),3.73 (3H, s, 4,-ArOCH3), 3 [0184] 1HNMR (300MHz, DMS0_d6), δ (ppm): 12.45 (1Η, brs, C00H), 7.67 (1Η, s, = CH), 6.88 (2H, s, 2, & 6, -ArH), 6.54 ( 1H, s, 5, _ArH), 6.49 (2H, s, 2 ,, & 6 "_ArH), 3.73 (3H, s, 4, -ArOCH3), 3

• 71 (6H, s, 3” &5” -ArOCH3),3.68 (3H, s, 4” -ArOCH3),3.36 (3H, s, 3' -ArOCH3).[0185] N-(2,3,4,6-四_0_ 乙酰基-1-脱氧-β _D_ 吡喃葡萄糖基)-(E) _3_ (3',4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-17) • 71 (6H, s, 3 "& 5" -ArOCH3), 3.68 (3H, s, 4 "-ArOCH3), 3.36 (3H, s, 3 '-ArOCH3). [0185] N- (2,3,4 , 6-acetyl-1-deoxy-four _0_ -β _D_ glucopyranosyl) - (E) _3_ (3 ', 4' - dimethoxyphenyl) -2- (3 ', 4', 5 "_ trimethoxyphenyl) acrylamide (1-17)

[0186] G1-NH2 (0.9g, 2.6mmol),Ie (0.97g, 2.6mmol)经同I_1 操作得淡黄色固体0.5g,收率27.4%, mp82-840C ; [0186] G1-NH2 (0.9g, 2.6mmol), Ie (0.97g, 2.6mmol) by operating with I_1 light yellow solid 0.5g, yield 27.4%, mp82-840C;

[0187] 1H-Nmr(SoomHz1CDCI3) δ (ppm): 7.77 (1H, s, -CH=), 6.85 (1Η, dd, J=L 8Hz, J=8.4Hz, 6'-ArH),6.74 (1H, d, J=8.4Hz, 5'_ArH),6.46 (3H, s, 2',2”&6”-ArH),6.32 (1H, d, J=9.2Hz, NH),5.39 〜5.31 (2H, m, J=9.5Hz, Hl, H-2),5.05 (1H, t, J=9.7Hz, H-3),4.84 (1H, t, J=9.5Hz, H-4),4.34 (1H, dd, J=4.1Hz, J=12.6Hz, H_6a),4.11 〜4.06 (1H, m, H_6b),3.92 (3H, s, 4,-ArOCH3),3.89 〜3.88 (1H, m, H-5),3.85 (6H, s, 3 ”&5 ”_ArOCH3), 3.81 (3H, s, 4”_Ar0CH3),3.49 (3H, s,3,-ArOCH3), 2.08, 2.02 (each3H, each s, 2 X OAc), 1.98 (6H, s, 2 X OAc); [0187] 1H-Nmr (SoomHz1CDCI3) δ (ppm): 7.77 (1H, s, -CH =), 6.85 (1Η, dd, J = L 8Hz, J = 8.4Hz, 6'-ArH), 6.74 (1H , d, J = 8.4Hz, 5'_ArH), 6.46 (3H, s, 2 ', 2 "& 6" -ArH), 6.32 (1H, d, J = 9.2Hz, NH), 5.39 ~5.31 (2H, m, J = 9.5Hz, Hl, H-2), 5.05 (1H, t, J = 9.7Hz, H-3), 4.84 (1H, t, J = 9.5Hz, H-4), 4.34 (1H, dd, J = 4.1Hz, J = 12.6Hz, H_6a), 4.11 ~4.06 (1H, m, H_6b), 3.92 (3H, s, 4, -ArOCH3), 3.89 ~3.88 (1H, m, H-5) , 3.85 (6H, s, 3 "& 5" _ArOCH3), 3.81 (3H, s, 4 "_Ar0CH3), 3.49 (3H, s, 3, -ArOCH3), 2.08, 2.02 (each3H, each s, 2 X OAc) , 1.98 (6H, s, 2 X OAc);

[0188] IR(cm_1):2941 (CH),1753 (ester, C=0), 1676 (amide, C=0), 1581,1514,1383,1232 (OCH3), 1127 (OAc),1038 (0CH3) [0188] IR (cm_1): 2941 (CH), 1753 (ester, C = 0), 1676 (amide, C = 0), 1581,1514,1383,1232 (OCH3), 1127 (OAc), 1038 (0CH3 )

[0189] MS (ESI (+) 70eV, m/z): 704.3 [M+H] +; [0189] MS (ESI (+) 70eV, m / z): 704.3 [M + H] +;

[0190] HR-MS (1: TOF MS ES (+) 7.89e3): Calc.Mass: 726.2374, C34H41NO15Na.FoundMass: 726.2378.[0191] 实施例10 [0190] HR-MS (1: TOF MS ES (+) 7.89e3): Calc.Mass: 726.2374, C34H41NO15Na.FoundMass:. 726.2378 [0191] Example 10

[0192] N-(2,3,4,6-四_0_ 乙酰基-1-脱氧_ β _D_ 吡喃半乳糖基)-(E) _3_ (3,,4' - 二甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-18)的制备 [0192] N- (2,3,4,6- four _0_-acetyl-1-deoxy-_ β _D_-galactopyranosyl) - (E) _3_ (3,, 4 '- dimethoxyphenyl ) -2- ("4" 5 "_ trimethoxyphenyl) acrylamide (1-18) of Preparation 3,

[0193] G2-NH2 (0.9g, 2.6mmol),Ie (0.97g, 2.6mmol)经同I_1 操作得淡黄色固体0.6g,收率32.9%, mp72-740C ; [0193] G2-NH2 (0.9g, 2.6mmol), Ie (0.97g, 2.6mmol) obtained by the same operation as a pale yellow solid I_1 0.6g, yield 32.9%, mp72-740C;

[0194] 1H-NMR (500MHz, CDCl3) δ (ppm):7.75 (1H, s, -CH=), 6.83 (1Η, dd, J=L 85Hz, J=8.45Hz, 6'-ArH),6.73 (1H, d, J=8.45Hz, 5'-ArH),6.46 (2H, s, 2”&6”_ArH),6.45 (1H, d, J=2Hz, 2,_krH),6.31 (1H, d, J=9.3Hz, NH),5.42 (1H, d, J=3.4Hz, H_4),5.34 (1H, t, J=9.3Hz, Hl),5.13 (1H,dd, J=3.5Hz, J=10.3Hz, H-3),4.97 (1H, t, J=9.8Hz, H-2),4.11 〜4.08 (3H, m, H_6a, H_6b andH-5), 3.91 ( 3H, s, 4' -ArOCH3),3.83 (6H, s, 3 ”&5 ”_Ar0CH3),3.82 (3H, s, 4”_Ar0CH3),3.47 (3H,s, 3,-ArOCH3), 2.12, 2.02, 1.98, 1.95 (each3H, each s, 4 X OAc); [0194] 1H-NMR (500MHz, CDCl3) δ (ppm): 7.75 (1H, s, -CH =), 6.83 (1Η, dd, J = L 85Hz, J = 8.45Hz, 6'-ArH), 6.73 (1H, d, J = 8.45Hz, 5'-ArH), 6.46 (2H, s, 2 "& 6" _ArH), 6.45 (1H, d, J = 2Hz, 2, _krH), 6.31 (1H, d, J = 9.3Hz, NH), 5.42 (1H, d, J = 3.4Hz, H_4), 5.34 (1H, t, J = 9.3Hz, Hl), 5.13 (1H, dd, J = 3.5Hz, J = 10.3 Hz, H-3), 4.97 (1H, t, J = 9.8Hz, H-2), 4.11 ~4.08 (3H, m, H_6a, H_6b andH-5), 3.91 (3H, s, 4 '-ArOCH3) , 3.83 (6H, s, 3 "& 5" _Ar0CH3), 3.82 (3H, s, 4 "_Ar0CH3), 3.47 (3H, s, 3, -ArOCH3), 2.12, 2.02, 1.98, 1.95 (each3H, each s, 4 X OAc);

[0195] IR(cm_1):2938 (CH),1750 (ester, C=0), 1677 (amide, C=0), 1580,1514,1371, [0195] IR (cm_1): 2938 (CH), 1750 (ester, C = 0), 1677 (amide, C = 0), 1580,1514,1371,

1235 (OCH3), 1127 (OAc),1052 (OCH3) 1235 (OCH3), 1127 (OAc), 1052 (OCH3)

[0196] MS (ESI (+) 70eV, m/z): 704.2 [M+H] +; [0196] MS (ESI (+) 70eV, m / z): 704.2 [M + H] +;

[0197] HR-MS (1: TOF MS ES (+) 4.64e4): Calc.Mass: 726.2374, C34H41NO15Na.FoundMass: 726.2380.[0198] 实施例11[0199] N-(2,3,4,6-四-O-乙酰基-1-脱氧-β _D_ 吡喃葡萄糖基)-(E) _3_ (3' -硝基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-21)的制备 [0197] HR-MS (1: TOF MS ES (+) 4.64e4): Calc.Mass: 726.2374, C34H41NO15Na.FoundMass:. 726.2380 [0198] Example 11 [0199] N- (2,3,4,6 - four -O- -β _D_-acetyl-1-deoxy-glucopyranosyl) - (E) _3_ (3 '- nitro-4'-methoxyphenyl) -2- (3 ", 4", Preparation 5 "_ trimethoxyphenyl) acrylamide (1-21) is

[0200] (E)-3-(3硝基-4' -甲氧基)苯基-2-(3”,4”,5”_三-甲氧基)苯基-丙烯酸(If) [0200] (E) -3- (3-nitro-4 '- methoxy) phenyl-2- (3', 4 ', 5' _ three - methoxy) phenyl - acrylic acid (If)

[0201] 在IOOml三颈瓶中加入3,4, 5_三甲氧基苯乙酸(2.4g, 10.6mmol)、3_硝基-4-甲氧基苯甲醒(1.92g, 10.6mmol)、2.4mI三乙胺和24ml乙酸酐,搅拌升温至140C,反应12h,停止加热,滴加浓盐酸14.4ml,室温下过夜。 [0201] In IOOml three-necked flask was added 3,4, 5_ trimethoxy phenylacetic acid (2.4g, 10.6mmol), 3_-nitro-4-methoxy-benzoic awake (1.92g, 10.6mmol), 2.4mI triethylamine and 24ml of acetic anhydride, warmed with stirring to 140 C, the reaction 12h, heating was stopped, concentrated hydrochloric acid was added dropwise 14.4ml, at room temperature overnight. 有土黄色固体析出,停止反应,过滤,固体用约150ml乙醇重结晶,得黄色针状物纯品1.86g,产率为45.0%,mp225-227C (文献值:2230C [Bioorg.Med.Chem.,2005,13(11):3853 〜3864.]) There khaki solid precipitation, to stop the reaction, filtered and the solids with about 150ml recrystallized from ethanol to give yellow needles pure 1.86g, yield 45.0%, mp225-227 C (literature values: 2230C [Bioorg.Med. Chem, 2005,13 (11):. 3853 ~3864]).

[0202] N- (2,3,4,6_ 四_0_ 乙酰基-1-脱氧_ β -D-吡喃葡萄糖基)_ (E) _3_ (3' -硝基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-21) [0202] N- (2,3,4,6_ four _0_-acetyl-1-deoxy-_ β -D- glucopyranosyl) _ (E) _3_ (3 '- nitro-4'-methoxy phenyl) -2- (3 ", 4", 5 "_ trimethoxyphenyl) acrylamide (1-21)

[0203] G1-NH2 (0.9g, 2.6mmol),If (1.0g, 2.6mmol)经同1-1 操作得鹅黄色固体0.75g,收$40.6%, mp80-82 0C ; [0203] G1-NH2 (0.9g, 2.6mmol), If (1.0g, 2.6mmol) by the same 1-1 operation was light yellow solid 0.75g, received $ 40.6%, mp80-82 0C;

[0204] 1H-NmrGoomHz, CDCl3) δ (ppm): 7.73 (m, s, -CH=),7.53 (m, d, J=2.lHz, 2,-ArH),7.20 (1H, dd, J=2.1 Hz, J=8.85Hz, 6'_ArH),6.90 (1H, d, J=8.82Hz, 5'_ArH),6.40 (2H, s, 2,,&6,,_ArH),5.35 (1H, d, J=9.3Hz, NH),5.29 (1H, d, J=9.5Hz, Hl), 5.08 — 5.02 (1H, m, H-3),4.83 (1H,t, J=9.5Hz, H-2), 4.35 — 4.30 (1H, m, H_4),4.09 (1H, dd, J=4.6Hz, J=12.6Hz, H_6a), 3.98 — [0204] 1H-NmrGoomHz, CDCl3) δ (ppm): 7.73 (m, s, -CH =), 7.53 (m, d, J = 2.lHz, 2, -ArH), 7.20 (1H, dd, J = 2.1 Hz, J = 8.85Hz, 6'_ArH), 6.90 (1H, d, J = 8.82Hz, 5'_ArH), 6.40 (2H, s, 2 ,, & 6 ,, _ ArH), 5.35 (1H, d , J = 9.3Hz, NH), 5.29 (1H, d, J = 9.5Hz, Hl), 5.08 - 5.02 (1H, m, H-3), 4.83 (1H, t, J = 9.5Hz, H-2 ), 4.35 - 4.30 (1H, m, H_4), 4.09 (1H, dd, J = 4.6Hz, J = 12.6Hz, H_6a), 3.98 -

3.96 (1H, m, H_6b),3.98 (3H, s, 4' -ArOCH3),3.93 (3H, s, 4”_Ar0CH3),3.88 (1H, s, H-5), 3.85 (6H, s, 3”&5”-ArOCH3), 2.08,2.02 (each3H, each s, 2 X OAc) 1.98,(6H, s, 2 X OAc); 3.96 (1H, m, H_6b), 3.98 (3H, s, 4 '-ArOCH3), 3.93 (3H, s, 4 "_Ar0CH3), 3.88 (1H, s, H-5), 3.85 (6H, s, 3 "& 5" -ArOCH3), 2.08,2.02 (each3H, each s, 2 X OAc) 1.98, (6H, s, 2 X OAc);

[0205] IR(cm_1):2943 (CH),1752 (ester, C=O), 1678 (amide, C=O), 1615,1533 (NO2), 1236 (OCH3), 1127 (OAc),103.9 (OCH3) [0205] IR (cm_1): 2943 (CH), 1752 (ester, C = O), 1678 (amide, C = O), 1615,1533 (NO2), 1236 (OCH3), 1127 (OAc), 103.9 ( OCH3)

[0206] MS (ESI(+)70eV, m/z): 719.3 [M+H]+ ;MS (ESI (-) 70V, m/z): 717.2 [MH]-; [0206] MS (ESI (+) 70eV, m / z): 719.3 [M + H] +; MS (ESI (-) 70V, m / z): 717.2 [MH] -;

[0207] HR-MS (1: TOF MS ES (+) 2.98e4): Calc.Mass: 741.2119,C33H38N2O16Na.FoundMass:741.2124.[0208] 实施例12 [0207] HR-MS (1: TOF MS ES (+) 2.98e4): Calc.Mass: 741.2119, C33H38N2O16Na.FoundMass:. 741.2124 [0208] Example 12

[0209] N- (2,3,4,6-四-0-乙酰基-1-脱氧-β -D-吡喃半乳糖基)_ (E) _3_ (3 ' -硝基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-22)的制备 [0209] N- (2,3,4,6- tetra-O-acetyl-1-deoxy -β -D- galactopyranosyl) _ (E) _3_ (3 '- nitro-4'- methoxyphenyl) -2- ("4" 5 "_ trimethoxyphenyl) acrylamide (1-22) of Preparation 3,

[0210] G2-NH2 (0.9g, 2.6mmol),If (1.0g, 2.6mmol)经同1-1 操作得鹅黄色固体0.8g,收率43.3%, mp100-102 C ; [0210] G2-NH2 (0.9g, 2.6mmol), If (1.0g, 2.6mmol) by the same 1-1 operation was light yellow solid 0.8g, yield 43.3%, mp100-102 C;

[0211] 1H-NmrGoomHz, CDCl3) δ (ppm):7.75 (m, s, -CH=),7.51 (m, d, J=2.lHz, 2,-ArH),7.23 (1H, dd, J=2.1 Hz, J=8.9Hz, 6'_ArH),6.91 (1H, d, J=8.9Hz, 5'_ArH),6.42 (2H, s, 2,,&6”_ArH),6.39 (1H, d, J=9.4Hz, NH),5.44 (1H, d, J=3.3Hz, H_4),5.34 (1H, t, J=9.2,Hl),5.14 (1H, dd, J=3.4Hz, J=10.3Hz, H-3),4.98 (1H, t, J=9.8Hz, H-2), 4.13 — 4.09 (3H, m, H-5, H-6a&H_6b) [0211] 1H-NmrGoomHz, CDCl3) δ (ppm): 7.75 (m, s, -CH =), 7.51 (m, d, J = 2.lHz, 2, -ArH), 7.23 (1H, dd, J = 2.1 Hz, J = 8.9Hz, 6'_ArH), 6.91 (1H, d, J = 8.9Hz, 5'_ArH), 6.42 (2H, s, 2 ,, & 6 "_ArH), 6.39 (1H, d, J = 9.4Hz, NH), 5.44 (1H, d, J = 3.3Hz, H_4), 5.34 (1H, t, J = 9.2, Hl), 5.14 (1H, dd, J = 3.4Hz, J = 10.3Hz , H-3), 4.98 (1H, t, J = 9.8Hz, H-2), 4.13 - 4.09 (3H, m, H-5, H-6a & H_6b)

,3.97 (3H, s, 4'-ArOCH3),3.93 (3H, s, 4”_Ar0CH3),3.86 (6H, s, 3 ”&5 ”_Ar0CH3), 2.17, 2.04,2.00, 1.93 (each3H, each s, 4 X OAc); , 3.97 (3H, s, 4'-ArOCH3), 3.93 (3H, s, 4 "_Ar0CH3), 3.86 (6H, s, 3" & 5 "_Ar0CH3), 2.17, 2.04,2.00, 1.93 (each3H, each s, 4 X OAc);

[0212] IR(cm_1):2941 (CH),1750 (ester, C=0), 1680 (amide, C=0), 1615,1533 (NO2), 1371,1231 (OCH3), 1127 (OAc), 1085 (OCH3) [0212] IR (cm_1): 2941 (CH), 1750 (ester, C = 0), 1680 (amide, C = 0), 1615,1533 (NO2), 1371,1231 (OCH3), 1127 (OAc), 1085 (OCH3)

[0213] MS (ESI(+)70eV, m/z): 719.3 [M+H]+ ; MS (ESI (-) 70V, m/z):717.4[Μ_ΗΓ; [0213] MS (ESI (+) 70eV, m / z): 719.3 [M + H] +; MS (ESI (-) 70V, m / z): 717.4 [Μ_ΗΓ;

[0214] HR-MS (1: TOF MS ES (+) 1.98e4): Calc.Mass: 741.2119,C33H38N2O16Na.FoundMass: 741.2123.[0215] 实施例13 [0214] HR-MS (1: TOF MS ES (+) 1.98e4): Calc.Mass: 741.2119, C33H38N2O16Na.FoundMass:. 741.2123 [0215] Example 13

[0216] N-(2, 3,4, 6-四-O-乙酰基-1-脱氧-β _D_ 吡喃葡萄糖基)-(E) _3_ (3' -氨基-4'-甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-25)的制备 [0216] N- (2, 3,4, 6- four -O- -β _D_-acetyl-1-deoxy-glucopyranosyl) - (E) _3_ (3 '- amino-4'-methoxyphenoxy yl) -2- ("4" 5 "_ trimethoxyphenyl) acrylamide (1-25) of Preparation 3,

[0217]将 1-21 (0.6g, 0.83mmol)溶于20ml 乙醇,NH4Cl (0.32g, 5.98mmol)溶于6ml 水,合并两者,加入还原Fe粉(0.24g, 4.3mmol),升温回流3.5h,停止反应,用娃藻土滤除Fe粉,同时用乙醇洗涤滤渣,旋干滤液,分别加乙酸乙酯30ml,水20ml,分出有机层,并依次用水(2 X 20ml)洗,饱和NaHCO3 (IX 30ml)洗,饱和NaCl (2 X 30ml)洗,无水硫酸镁干燥4h,过滤,旋干,得棕黄色粘稠状粗品0.6g,硅胶柱层析(二氯甲烷/甲醇=200/1),得黄色固体 [0217] The 1-21 (0.6g, 0.83mmol) was dissolved in 20ml of ethanol, NH4Cl (0.32g, 5.98mmol) dissolved in 6ml water, both combined, added to reduce Fe powder (0.24g, 4.3mmol), heated at reflux 3.5h, the reaction was stopped, filtered with diatomaceous earth baby Fe powder, and the filter residue was washed with ethanol, spin dry the filtrate were added ethyl acetate 30ml, water 20ml, and the organic layer was separated, and washed successively with water (2 X 20ml) washed, saturated NaHCO3 (IX 30ml) washed with saturated NaCl (2 X 30ml), dried over anhydrous magnesium sulfate 4h, filtered, spin dried to give brown viscous crude 0.6g, silica gel column chromatography (methylene chloride / methanol = 200/1) to give a yellow solid

0.45g,收率78.3%,m.ρ.90-92 O ; 0.45g, yield 78.3%, m.ρ.90-92 O;

[0218] 1H-NMR (500MHz, DMS0-d6) δ (ppm): 7.61 (1H, d, J=9.3Hz, NH), 7.29 (1H, s, -CH=), 6.83 〜6.74 (1H, m, 6,-ArH), 6.63 (1H, d, J=8.5Hz, 5,-ArH), 6.46 (1H, s, 2,-ArH), 6.41(2H, s, 2,,&6,,-ArH),5.47 (1H, t, J=9.3Hz, Hl),5.36 (1H, t, J=9.45Hz, H-2),5.00 (1H, t, J=9.4Hz, H-3),4.87 (1H, t, J=9.65Hz, H_4),4.63 (2H, s, NH2), 4.17 〜4.15 (1H, m, H_6a), 4.09 〜4.04 (2H, m, H-6b &H_5),3.74 (3H, s, 4' -ArOCH3), 3.71 (3H, s, 4”_Ar0CH3),3.70 (6H, s, 3”&5”_ArOCH3), 1.99, 1.98, 1.95, 1.93 (each3H, each s, 4 X OAc); [0218] 1H-NMR (500MHz, DMS0-d6) δ (ppm): 7.61 (1H, d, J = 9.3Hz, NH), 7.29 (1H, s, -CH =), 6.83 ~6.74 (1H, m , 6, -ArH), 6.63 (1H, d, J = 8.5Hz, 5, -ArH), 6.46 (1H, s, 2, -ArH), 6.41 (2H, s, 2 ,, & 6 ,, - ArH ), 5.47 (1H, t, J = 9.3Hz, Hl), 5.36 (1H, t, J = 9.45Hz, H-2), 5.00 (1H, t, J = 9.4Hz, H-3), 4.87 ( 1H, t, J = 9.65Hz, H_4), 4.63 (2H, s, NH2), 4.17 ~4.15 (1H, m, H_6a), 4.09 ~4.04 (2H, m, H-6b & H_5), 3.74 (3H, s, 4 '-ArOCH3), 3.71 (3H, s, 4 "_Ar0CH3), 3.70 (6H, s, 3" & 5 "_ArOCH3), 1.99, 1.98, 1.95, 1.93 (each3H, each s, 4 X OAc);

[0219] IR(cm_1): 3407 (NH2),2941 (CH),1753 (ester, C=O), 1677 (amide, C=O), 1582,1514, [0219] IR (cm_1): 3407 (NH2), 2941 (CH), 1753 (ester, C = O), 1677 (amide, C = O), 1582,1514,

1236 (OCH3), 1126 (OAc),1037 (OCH3) 1236 (OCH3), 1126 (OAc), 1037 (OCH3)

[0220] MS (ESI (+) 70eV, m/z): 689.3 [M+H] +; [0220] MS (ESI (+) 70eV, m / z): 689.3 [M + H] +;

[0221] HR-MS (1: TOF MS ES (+) 2.31e4): Calc.Mass: 689.2558,C33H41N2O14.FoundMass: 689.2563.[0222] 实施例14 [0221] HR-MS (1: TOF MS ES (+) 2.31e4): Calc.Mass: 689.2558, C33H41N2O14.FoundMass:. 689.2563 [0222] Example 14

[0223] N-(1-脱氧-β-D-吡喃葡萄糖基)-(E)-3_(3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-29)的制备 [0223] N- (1- deoxy -β-D- glucopyranosyl) - (E) -3_ (3 '- hydroxy - 4' - methoxyphenyl) -2- (3 ", 4", Preparation 5 "_ trimethoxyphenyl) acrylamide (1-29) is

[0224] 1-1 (0.4g, 0.58mmol)溶于5ml甲醇钠/甲醇溶液,室温搅拌4h,停止反应,调节pH值到6,将溶液旋干,粗品用硅胶柱层析(二氯甲烷/甲醇=10/1),得微黄色纯品0.20g,产率为66.1%,mp125 〜127 O ; [0224] 1-1 (0.4g, 0.58mmol) was dissolved in 5ml sodium methoxide / methanol solution was stirred at room temperature 4h, the reaction was stopped, the pH adjusted to 6, and the solution was spin-dried, the crude product is purified by silica gel column chromatography (methylene chloride / methanol = 10/1) to give a slightly yellow pure 0.20g, yield 66.1%, mp125 ~127 O;

[0225] 1H-NMR (500MHz, DMS0_d6) δ (ppm): 8.87 (1H, s, -ArOH),7.62 (1H, d, J=9.0Hz, NH),7 [0225] 1H-NMR (500MHz, DMS0_d6) δ (ppm): 8.87 (1H, s, -ArOH), 7.62 (1H, d, J = 9.0Hz, NH), 7

• 30 (1H, s, -CH=),6.79 (1H, d, J=8.5Hz, 5'-ArH),6.55 (1H, dd, J=2.0Hz, J=8.4Hz, 6'-ArH),6.52 (1H, d, J=2.1Hz, 2'-ArH),6.47 (2H, s, 2”&6”_ArH),4.96 〜4.81 (3H, m, OH-2, 3&4),4.45 〜 • 30 (1H, s, -CH =), 6.79 (1H, d, J = 8.5Hz, 5'-ArH), 6.55 (1H, dd, J = 2.0Hz, J = 8.4Hz, 6'-ArH) , 6.52 (1H, d, J = 2.1Hz, 2'-ArH), 6.47 (2H, s, 2 "& 6" _ArH), 4.96 ~4.81 (3H, m, OH-2, 3 & 4), 4.45 ~

4.43 (1H, m, OH-6),3.80 〜3.75 (2H, m, H-1and H-2),3.73 (3H, s, 4,-ArOCH3),3.72 (3H, s, 4”-ArOCH3),3.68 (6H, s, 3 ”&5 ”_ArOCH3),3.44 〜3.40 (1H, m, H-3),3.21 〜3.12 (3H, m, H-5, H_6aand H-6b),3.07 〜3.03 (1H, m, H_4); 4.43 (1H, m, OH-6), 3.80 ~3.75 (2H, m, H-1and H-2), 3.73 (3H, s, 4, -ArOCH3), 3.72 (3H, s, 4 "-ArOCH3) , 3.68 (6H, s, 3 "& 5" _ArOCH3), 3.44 ~3.40 (1H, m, H-3), 3.21 ~3.12 (3H, m, H-5, H_6aand H-6b), 3.07 ~3.03 (1H , m, H_4);

[0226] 1H-NMR (300MHz, DMS0_d6+D20) δ (ppm):7.31 (1H, s, -CH=), 6.81 (1H, d, J=8.6Hz, 5'-ArH),6.58 (1H, dd, J=L 9Hz, J=8.6Hz, 6'_ArH) ,6.51 (1H, d, J=L 9Hz, 2'_ArH),6.47 (2H, s, 2”&6” -ArH),4.83 (1H, d, J=8.7Hz, NH),3.80 〜3.78 (2H, m, H-1and H-2),3.75 (3H, s, 4,-ArOCH3),3.74 (3H, s, 4”_Ar0CH3),3.69 (6H, s, 3 ”&5 ”_ArOCH3),3.46 〜3.41 (1H, m, H-3),3.24 〜3.19 (3H, m, H-5, H_6aand H_6b),3.10 〜3.08 (1H, m, H_4); [0226] 1H-NMR (300MHz, DMS0_d6 + D20) δ (ppm): 7.31 (1H, s, -CH =), 6.81 (1H, d, J = 8.6Hz, 5'-ArH), 6.58 (1H, dd, J = L 9Hz, J = 8.6Hz, 6'_ArH), 6.51 (1H, d, J = L 9Hz, 2'_ArH), 6.47 (2H, s, 2 "& 6" -ArH), 4.83 (1H , d, J = 8.7Hz, NH), 3.80 ~3.78 (2H, m, H-1and H-2), 3.75 (3H, s, 4, -ArOCH3), 3.74 (3H, s, 4 "_Ar0CH3), 3.69 (6H, s, 3 "& 5" _ArOCH3), 3.46 ~3.41 (1H, m, H-3), 3.24 ~3.19 (3H, m, H-5, H_6aand H_6b), 3.10 ~3.08 (1H, m, H_4);

[0227] IR(cm_1): 3411 (OH),2937 (CH),1654 (amide, C=0), 1583,1510,1240 (OCH3), 1125,I079 (OCH3),1026 [0227] IR (cm_1): 3411 (OH), 2937 (CH), 1654 (amide, C = 0), 1583,1510,1240 (OCH3), 1125, I079 (OCH3), 1026

[0228] MS (ESI(+)70eV, m/z):522.1 [M+H]+; MS (ESI (-) 70V, m/z): 556.3 [M+C1]_; [0228] MS (ESI (+) 70eV, m / z): 522.1 [M + H] +; MS (ESI (-) 70V, m / z): 556.3 [M + C1] _;

[0229] HR-MS (1: TOF MS ES (+) 5.126e4): Calc.Mass: 544.1795, C25H31NO11Na.FoundMass: 544.1799.[0230] 实施例15 [0229] HR-MS (1: TOF MS ES (+) 5.126e4): Calc.Mass: 544.1795, C25H31NO11Na.FoundMass:. 544.1799 [0230] Example 15

[0231] N-(1-脱氧-β-D-吡喃半乳糖基)-(E)-3_(3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-30)的制备 [0231] N- (1- deoxy -β-D- galactopyranosyl) - (E) -3_ (3 '- hydroxy - 4' - methoxyphenyl) -2- (3 ", 4" , 5 "_ trimethoxyphenyl) acrylamide (1-30) was prepared

[0232]取 1-2 (0.4g, 0.58mmol),经同1-29 操作得微黄色固体0.22g,收率72.7%,mp126-128C ; 1H-NMR (500MHz, DMS0_d6) δ (ppm):8.87 (1H, s, -ArOH),7.42 (1H, d, J=9.1Hz, NH),7 [0232] Take 1-2 (0.4g, 0.58mmol), after the operation was 1-29 with a slightly yellow solid 0.22g, yield 72.7%, mp126-128 C; 1H-NMR (500MHz, DMS0_d6) δ (ppm ): 8.87 (1H, s, -ArOH), 7.42 (1H, d, J = 9.1Hz, NH), 7

• 33 (1H, s, -CH=),6.79 (1H, d, J=8.5Hz, 5'-ArH),6.55 (1H, dd, J=2.0Hz, J=8.5Hz, 6'-ArH),6.51 (1H, d, J=2.0Hz, 2,-ArH),6.49 (2H, s, 2”&6”_ArH),4.83 〜4.78 (2H, m, OH-2, 3),4.72 〜 • 33 (1H, s, -CH =), 6.79 (1H, d, J = 8.5Hz, 5'-ArH), 6.55 (1H, dd, J = 2.0Hz, J = 8.5Hz, 6'-ArH) , 6.51 (1H, d, J = 2.0Hz, 2, -ArH), 6.49 (2H, s, 2 "& 6" _ArH), 4.83 ~4.78 (2H, m, OH-2, 3), 4.72 ~

4.69 (1H, m, OH-4), 4.55 〜4.53 (1H, m, OH-6),4.27 (1H, d, J=5Hz, Hl),3.79 (1H, s, H_4),3.73 (3H, s, 4,-ArOCH3), 3.72 (3H, s, 4”-ArOCH3),3.69 (6H, s, 3” &5”-ArOCH3),3.67 〜 4.69 (1H, m, OH-4), 4.55 ~4.53 (1H, m, OH-6), 4.27 (1H, d, J = 5Hz, Hl), 3.79 (1H, s, H_4), 3.73 (3H, s, 4, -ArOCH3), 3.72 (3H, s, 4 "-ArOCH3), 3.69 (6H, s, 3" & 5 "-ArOCH3), 3.67 ~

3.66 (2H, m, H-2, H-3),3.43 〜3.40 (2H, m, H_6a and H_6b),3.36 〜3.35 (1H, m, H-5); 3.66 (2H, m, H-2, H-3), 3.43 ~3.40 (2H, m, H_6a and H_6b), 3.36 ~3.35 (1H, m, H-5);

[0233] 1H-匪R (300MHz, DMS0_d6+D20) δ (ppm):7.34 (1H, s, -CH=), 6.81 (1H, d, J=8.6Hz,5,-ArH),6.59 (1H, dd, J=2.0Hz, J=8.6Hz, 6,-ArH),6.51 (1H, d, J=2.0Hz, 2,-ArH),6.49 (2H,s, 2” &6” -ArH), 4.81 (1H, d, J=8.4Hz, NH),3.80 (1H, s, H_4),3.78 (1H, m, Hl),3.74 (3H, s,4' -ArOCH3),3.73 (3H, s, 4”_Ar0CH3),3.69 (6H, s, 3”&5”_Ar0CH3),3.67 (1H, s, H-2),3.48 〜3.46 (1H, m, H-3),3.45 〜3.42 (2H, m, H_6a and H_6b),3.40 〜3.39 (1H, m, H-5); [0233] 1H- bandit R (300MHz, DMS0_d6 + D20) δ (ppm): 7.34 (1H, s, -CH =), 6.81 (1H, d, J = 8.6Hz, 5, -ArH), 6.59 (1H , dd, J = 2.0Hz, J = 8.6Hz, 6, -ArH), 6.51 (1H, d, J = 2.0Hz, 2, -ArH), 6.49 (2H, s, 2 "& 6" -ArH), 4.81 (1H, d, J = 8.4Hz, NH), 3.80 (1H, s, H_4), 3.78 (1H, m, Hl), 3.74 (3H, s, 4 '-ArOCH3), 3.73 (3H, s, 4 "_Ar0CH3), 3.69 (6H, s, 3" & 5 "_Ar0CH3), 3.67 (1H, s, H-2), 3.48 ~3.46 (1H, m, H-3), 3.45 ~3.42 (2H, m, H_6a and H_6b), 3.40 ~3.39 (1H, m, H-5);

[0234] IR(cm_1):3416 (OH), 1651 (amide, C=O), 1583,1512,1411,1240 (OCH3),1125,1084(OCH3), 1024MS (ESI(+)70eV, m/z):522.1 [M+H]+ ; MS (ES 1(-) 70V, m/z): 556.3 [M+C1]_; [0234] IR (cm_1): 3416 (OH), 1651 (amide, C = O), 1583,1512,1411,1240 (OCH3), 1125,1084 (OCH3), 1024MS (ESI (+) 70eV, m / z): 522.1 [M + H] +; MS (ES 1 (-) 70V, m / z): 556.3 [M + C1] _;

[0235] HR-MS (1: TOF MS ES (+) 2.46e4): Calc.Mass: 544.1795, C25H31NO11Na.FoundMass:544.1800.[0236] 实施例16 [0235] HR-MS (1: TOF MS ES (+) 2.46e4): Calc.Mass: 544.1795, C25H31NO11Na.FoundMass:. 544.1800 [0236] Example 16

[0237] N-(2-脱氧_β -D-吡喃葡萄糖基)-(Ε)-3_(3' -羟基-4' -甲氧基苯基)-2-(3”,4”,5”_三甲氧基苯基)丙烯酰胺(1-31)的制备 [0237] N- (2- deoxy _β -D- glucopyranosyl) - (Ε) -3_ (3 '- hydroxy - 4' - methoxy-phenyl) -2- (3 ", 4", Preparation 5 "_ trimethoxyphenyl) acrylamide (1-31) is

[0238]取 1-3 (0.4g, 0.58mmol),经同1-29 操作得类白色固体0.16g,收率52.9%,mp122-124C。 [0238] Take 1-3 (0.4g, 0.58mmol), have been operating with 1-29 off-white solid 0.16g, yield 52.9%, mp122-124 C.

[0239] 实施例17 [0239] Example 17

[0240] N-(1-脱氧-β -D-吡喃半乳糖基)-(E) -3- (4,-甲氧基苯基)-2- (3”,4”,5,,-三甲氧基苯基)丙烯酰胺(1-34)的制备 [0240] N- (1- deoxy -β -D- galactopyranosyl) - (E) -3- (4, - methoxyphenyl) -2- (3 ', 4', 5 ,, trimethoxyphenyl) acrylamide (1-34) Preparation -

[0241]取 1-6 (0.39g, 0.58mmol),经同1-29 操作得微黄色固体0.18g,收率61.5%,mp109-112C。 [0241] Take 1-6 (0.39g, 0.58mmol), after the operation was 1-29 with a slightly yellow solid 0.18g, yield 61.5%, mp109-112 C.

[0242] 实施例18 [0242] Example 18

[0243] 片剂 [0243] Tablets

[0244] 取实施例1中所得化合物0.5g,淀粉2g,糊精Ig混合,用适量30%乙醇作湿润剂,制粒,压片。 [0244] Take the compound obtained in Example 1 0.5g, starch 2g, dextrin Ig mixed with an appropriate amount of 30% ethanol as wetting agents, granulating, tabletting.

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